Spontaneous Findings in the Reproductive System of Sexually Mature Male Cynomolgus Macaques.

Sexually mature nonhuman primates are often used in nonclinical safety testing when evaluating biopharmaceuticals; however, there is limited information in historical control databases or in the published literature on the spontaneous findings in the male reproductive system. This review evaluated digital slides from the male reproductive tract (testes, epididymides, prostate, and seminal vesicles) in sexually mature cynomolgus macaques (Macaca fascicularis; n = 255) from vehicle control groups in nonclinical toxicology studies and compared the observations with body weight, organ weight, and geographical origin. The most common microscopic findings were hypospermatogenesis and tubular dilatation in the testes; inflammatory cell infiltrate, cellular debris, and decreased sperm in the epididymides; inflammatory cell infiltrate and acinar dilatation in the prostate; and corpora amylacea and atrophy in the seminal vesicles. There were a few correlative observations in animals when grouped by weight or geographical origin: animals with lower terminal body weights (<5 kg) often displayed features of late puberty despite having sperm in the epididymis, while animals originating from Mauritius had a lower incidence of inflammatory cell infiltrates than those from Southeast Asia/China. This review provides incidence, descriptions, and photomicrographs of the common spontaneous microscopic findings in the reproductive system of mature male cynomolgus macaques.

A Novel Technique of Paravertebral Thoracic and Preperitoneal Analgesia Enhances Early Recovery After Oesophagectomy.

BACKGROUND: Excellent analgesia following oesophagectomy facilitates patient comfort, early extubation, physiotherapy and mobilisation, reduces post-operative complications and should enhance recovery. Thoracic epidural analgesia (TEA), the gold standard analgesic regimen for this procedure, is often associated with systemic hypotension treated with inotropes or fluid. This may compromise enhanced recovery and be complicated by anastomotic ischaemia or tissue oedema. METHODS: We report a novel analgesic regimen to reduce post-operative inotrope usage. Infusion of ropivicaine via bilateral preperitoneal and right paravertebral catheters was used. Patient-controlled epidural pethidine provided rescue analgesia (WC) (n = 21). A retrospective audit of inotrope requirement, mean pain scores, episodes of respiratory depression and excessive sedation, need for reintubation, reoperation in the first 5 post-operative days, time to mobilisation, time in intensive care, time in hospital and 30-day mortality were measured. These results were compared with those of an earlier patient group who received a thoracic epidural infusion of low-dose local anaesthetic and fentanyl (TEA) (n = 21). RESULTS: Inotrope use was reduced by 29% in the WC group (p = 0.03) and the mean intensive care stay reduced by 2.4 days (p = 0.03), as was reintubation rate (p = 0.01) and early mobilisation (p = 0.03). The pain score was comparable in both groups, and there was no difference in the other outcomes examined. CONCLUSION: The data demonstrated that it was possible to provide excellent post-oesophagectomy analgesia equivalent to thoracic epidural infusions of local anaesthetic with reduction in inotrope requirements, intensive care stay, more rapid mobilisation, facilitating enhanced recovery.

The Impact of Residual Neuromuscular Blockade, Oversedation, and Hypothermia on Adverse Respiratory Events in a Postanesthetic Care Unit: A Prospective Study of Prevalence, Predictors, and Outcomes.

BACKGROUND: Residual neuromuscular blockade (RNMB) has been linked to adverse respiratory events (AREs) in the postanesthetic care unit (PACU). However, these events are often not attributed to RNMB by anesthesiologists because they may also be precipitated by other factors including obstructive sleep apnea, opioids, or hypnotic agents. Many anesthesiologists believe RNMB occurs infrequently and is rarely associated with adverse outcomes. This study evaluated the prevalence and predictors of RNMB and AREs. METHODS: This prospective cohort study included 599 adult patients undergoing general anesthesia who received neuromuscular blocking agents. Baseline demographic, surgical, and anesthetic variables were collected. RNMB was defined as a train-of-four ratio below 0.90 measured by electromyography on admission to the PACU. AREs were defined based on the modified Murphy's criteria. RESULTS: RNMB was present in 186 patients (31% [95% confidence interval (CI), 27%-35%]) on admission to the PACU. One or more AREs were experienced by 97 patients (16% [95% CI 13-19]). AREs were more frequent in patients with RNMB (21% vs 14%, P = .033). RNMB was significantly associated with age (adjusted relative risk [RR], 1.17 [95% CI, 1.06-1.29] per 10-year increase), type of operation (adjusted RR, 0.59 [95% CI, 0.34-0.99] for laparoscopic surgery compared with open abdominal surgery), and duration of operation (adjusted RR, 0.59 [95% CI, 0.39-0.86] for ≥90 minutes compared with <90 minutes). Using multivariate logistic regression, AREs were found to be independently associated with decreased level of consciousness (adjusted RR, 4.76 [95% CI, 1.49-6.76] for unrousable/unconscious compared with alert/awake) and lower core temperature (adjusted RR, 1.43 [95% CI, 1.04-1.92] per 1°C decrease). Although univariate analysis found a significant association between AREs and RNMB, the significance became borderline after adjusting for other covariates (adjusted RR, 1.46 [95% CI, 0.99-2.08]). CONCLUSIONS: The prevalence of RNMB in the PACU was >30%. Older age, open abdominal surgery, and duration of operation <90 minutes were associated with increased risk of RNMB in our patients. Our RR estimate for AREs was highest for depressed level of consciousness. When AREs occur in the PACU, potentially preventable causes including RNMB, hypothermia, and reduced level of consciousness should be readily identified and treated appropriately. Delaying extubation until the patient is awake and responsive may reduce AREs.

An ipsilateral comparison of acceleromyography and electromyography during recovery from nondepolarizing neuromuscular block under general anesthesia in humans.

BACKGROUND: Residual neuromuscular block is defined as a mechanomyography (MMG) or electromyography (EMG) train-of-four (TOF) ratio <0.90, and is common in patients receiving neuromuscular blocking drugs. Objective neuromuscular monitoring is the only reliable way to detect and exclude residual neuromuscular block. Acceleromyography (AMG) is commercially available and easy to use in the clinical setting. However, AMG is not interchangeable with MMG or EMG. Currently, it is unclear what value must be reached by AMG TOF ratio to reliably exclude residual neuromuscular block. METHODS: During spontaneous recovery from neuromuscular block, we monitored TOF ratio on the same arm using AMG at the adductor pollicis and EMG at the first dorsal interosseus. AMG and EMG TOF ratios were compared by the Bland-Altman analysis for repeated measurements. The precision of each device was assessed by the repeatability coefficient. A small repeatability coefficient indicates high precision of the device. The agreement between the devices was assessed by the bias and the 95% limits of agreement. Small bias and narrow limits of agreement indicate strong agreement. We defined clinically acceptable agreement between AMG and EMG as a bias <0.025 and limits of agreement within -0.050 to 0.050, provided that the control comparison between EMG and itself can fulfill these criteria. RESULTS: In 26 patients, 261 comparisons between AMG and EMG were made. The repeatability coefficient of AMG and EMG were 0.094 (95% confidence interval [CI], 0.088-0.100) and 0.051 (95% CI, 0.048-0.055), respectively. The bias between AMG and EMG TOF ratio was 0.176 (95% CI, 0.162-0.190), with limits of agreement -0.045 to 0.396 (95% CI, -0.067 to 0.419). CONCLUSIONS: AMG is less precise than EMG and overestimates EMG TOF ratio by at least 0.15. The lack of agreement cannot be attributed to instrumental imprecision or the baseline difference between successive measurements during spontaneous recovery of neuromuscular function. Residual neuromuscular block cannot be excluded on reaching an AMG TOF ratio of 1.00.

Borehole Nuclear Magnetic Resonance Estimation of Specific Yield in a Fractured Granite Aquifer.

In this study, we introduce a novel field-based method to estimate specific yield (Sy ) in fractured, low-porosity granite aquifers using borehole nuclear magnetic resonance (bNMR). This method requires collecting a bNMR survey immediately following a pump test, which dewaters the near-borehole fractures. The residual water content measured from bNMR is interpreted as "bound" and represents the specific retention (Sr ) while the water drained by the pump is the Sy . The transverse relaxation cutoff time (T2C ) is the length of time that partitions the total porosity measured by bNMR into Sr and Sy . When applying a calibrated T2C , Sy equals the bNMR total porosity minus Sr ; thus, a calibrated T2C is required to determine Sy directly from NMR results. Based on laboratory experiments on sandstone cores, the default T2C is 33 ms; however, its applicability to fractured granite aquifers is uncertain. The optimal T2C based on our pumping test is 110 ± 25 ms. Applying this calibrated T2C on a saturated, A-type granite at our field site, we estimate the Sy to be 0.012 ± 0.005 m3 m-3 which is significantly different from the Sy (0.021 ± 0.005 m3 m-3 ) estimate using the default T2C of 33 ms. This Sy estimate falls within a range determined using traditional hydraulic testing at the same site. Using the conventional T2C (33 ms) for fractured granite leads to an inaccurate Sy ; therefore, it is essential to calibrate the bNMR T2C for the local site conditions prior to estimating Sy .

The Influence of Iron and Ligand Type on Plutonium Uptake in Two Strains of Hydroponically Grown Corn ( Zea Mays ).

ABSTRACT: This work investigates the uptake and root-shoot transport of plutonium (Pu) and iron (Fe) in corn ( Zea mays ) to gain insight into the Pu uptake pathway. Plutonium has no known biological function in plants yet may feasibly enter plants through the uptake pathway used by Fe (an essential nutrient), as these two elements have similar chemical properties. A series of experiments was conducted in which two hydroponically grown corn strains (one normal and one deficient in the transporter protein for Fe) were exposed to varying concentrations of complexed Pu and Fe. Results suggest that while Fe did inhibit Pu uptake to a certain extent, Pu was able to use alternative uptake pathways. In a 10 ppb Pu:1 ppb Fe hydroponic solution, all shoots had detectable shoot Pu concentrations compared to only 22% of plants when the Fe concentration was raised to 10 ppb. While root Pu accumulation was reduced for the corn strain deficient in the Fe transporter protein at lower Pu media concentrations, there were no differences at higher Pu concentrations, signifying the existence of substitute transport routes. A comparison of citrate and deferoxamine B (DFOB) ligand influence found that Pu complexed with DFOB remained in the roots of the plant, while movement of Pu into the shoots of the plant was more prevalent with the Pu-citrate complex. This study advances understanding of the behavior and mobility of Pu in the terrestrial environment and specifically the interactions between Pu and an essential nutrient in a common crop species.

Chronic vertebrobasilar insufficiency in subclavian steal syndrome.

Subclavian steal syndrome is a vascular disorder that consists of significant blood supply restriction with resultant insufficiency of the vertebrobasilar artery and the subclavian artery causing symptomatic insufficiency to the brain and upper extremity. It is important to recognize this condition in patients with subacute to chronic posterior circulation vascular insufficiency as early diagnosis and treatment can have good clinical outcomes (J Clin Neurosci. 2010;17:1339). CT angiogram of the head and neck should be considered in patients with chronic vertebrobasilar insufficiency to evaluate subclavian steal syndrome.

Medical training in private and public.

BACKGROUND: Globally, the need for medical student training to be undertaken in the private sector is likely to increase. In Australia, it has increased by 250 per cent in the last decade. Effective clinical education is highly dependent on the attitudes and willingness to participate of both patients and medical staff. We aimed to examine these attitudes in both private and public hospitals. METHODS: Patients and medical staff at a private and a public hospital in Sydney were surveyed during December 2016 and January 2017 to investigate attitudes to medical student training. Attitudes were compared between hospitals. We also compared recent attitudes in the private hospital with those obtained in 2012. RESULTS: Patients at the public hospital were significantly more likely to want a student present at a consultation than those at a private hospital. Public hospital doctors had more positive attitudes towards medical students than their private colleagues. The negative financial impact of teaching was more significant for those in private practice. Since 2012, attitudes of private hospital patients towards medical students became significantly more positive whereas doctors' attitudes became less positive. The expansion of clinical education into the private sector is likely to increase globally DISCUSSION: The willingness of patients to participate in medical student training in both public and private hospitals is encouraging for future expansion into the private sector. The reduced willingness amongst private hospital medical staff over time and, in comparison to public hospital staff, suggests a need to address barriers for staff in the private sector.

Geophysical Assessment of a Proposed Landfill Site in Fredericktown, Missouri.

In cooperation with the U.S. Environmental Protection Agency (EPA), the U.S. Geological Survey (USGS) collected numerous types of geophysical data at a site in Fredericktown, Missouri, in June 2018. Various geophysical surveys were collectively used to help evaluate the overall suitability of the site for use as a mine waste-soil and sediment repository, and to evaluate the suite of geophysical methods for rapid collection and preliminary assessment of sites with shallow sediments. Land-based geophysical methods, which included frequency-domain electromagnetic induction (FDEM), electrical resistivity tomography (ERT), horizontal-to-vertical spectral ratio passive seismic (HVSR), and shear-wave refraction, were used to determine the depths to crystalline bedrock and characterize the overlying unconsolidated sediments (or regolith). Water-borne FDEM profiles and forward-looking infrared (FLIR) thermal image surveys were conducted along the Fredericktown City Lake shoreline to identify locations of potential interactions between groundwater and surface water. Sediment temperature profilers were installed at two locations along the shoreline to characterize shallow unconsolidated sediment thermal properties and support the interpretation of the other geophysical surveys. Geophysical reconnaissance methods including the FDEM and HVSR methods, were used to rapidly evaluate the vertical and lateral extent of overburden, or unconsolidated sediments, overlying the bedrock at the site. The results of these methods were compared to reference geophysical methods of ERT and shear-wave refraction surveys that have greater accuracy and are more labor intensive and time-consuming. A goal of the project was the evaluation of the validity and reliability of this suite of reconnaissance geophysical methods as a means by which shallow (less than 3 meters (m)) sediments can be rapidly assessed. Two orthogonal ERT survey profiles, which used 28 electrodes spaced 1 m apart in dipole-dipole and combined Wenner-Schlumberger configurations, were collected to determine the subsurface resistivity. The results were inverted to produce electrical resistivity profiles that were compared to the FDEM and HVSR survey results. The FDEM data were collected along cleared paths through the proposed disposal cell locations. The data were inverted to generate depth-dependent estimates of electrical conductivity along the transects. An analysis of the depth of investigation (DOI) indicated the FDEM imaged to depths of about 3 m below land surface. The ERT, FDEM, and HVSR indicated the depth to crystalline bedrock was approximately 1.5 m below land surface with shallower and deeper areas. Results from this investigation indicate this suite of methods will likely perform well at sites with shallow depths to bedrock and strong conductivity and acoustic impedance contrasts, where the FDEM and HVSR methods can provide estimates of the depth to bedrock, and ERT and shear-wave refraction surveys might not be worth the added time and expense.

Long-Term Treatment and Survival in Three Apparently Immunocompetent Dogs with Disseminated Fungal Infection Caused by Phialosimplex caninus.

Disseminated fungal infections cause morbidity and mortality in dogs. The prognosis varies depending on the infecting agent. Phialosimplex caninus is a recently recognized type of hyalohyphomyces. Knowledge regarding the clinical course of P caninus infection in dogs is limited to two previous case reports. The clinical features, diagnostic findings, responses to medical therapy, and long-term outcomes of three dogs with disseminated P caninus are presented in this study. All dogs had improved quality of life once itraconazole administration, with or without terbinafine, was instituted. Long-term disease remission was maintained even after discontinuation of antifungal therapy in a single dog.

Pneumothorax: Laparoscopic Intraoperative Management During Fundoplication Facilitates Management of Cardiopulmonary Instability and Surgical Exposure.

INTRODUCTION: Intraoperative pneumothorax may complicate surgery by obscuring surgical view and cause cardiorespiratory instability during fundoplication with large hiatus hernia. Proactive intraoperative treatment may reduce conversion and drain insertion and facilitate timely completion of surgery. MATERIALS AND METHODS: The authors present effective surgical and anesthetic measures to alleviate pneumothorax, which are helpful for hemodynamic stability and surgical visibility. CONCLUSION: Pneumothorax can complicate surgery by reducing surgical vision and causing cardiorespiratory instability. There is no requirement for laparoscopic or intercostal drainage. The authors provide various techniques to control intraoperative pneumothorax.

Analysis of aeromedical retrieval coverage using elliptical isochrones: An evaluation of helicopter fleet size configurations in Scotland.

BACKGROUND: Trauma systems in remote and rural regions often rely on helicopter emergency medical services to facilitate access to definitive care. The siting of such resources is key, but often relies on simplistic modeling of coverage, using circular isochrones. Scotland is in the process of implementing a national trauma network, and there have been calls for an expansion of aeromedical retrieval capacity. The aim of this study was to analyze population and area coverage of the current retrieval service configuration, with three aircraft, and a configuration with an additional helicopter, in the North East of Scotland, using a novel methodology. Both overall coverage and coverage by physician-staffed aircraft, with enhanced clinical capability, were analyzed. METHODS: This was a geographical analysis based on calculation of elliptical isochrones, which consider the "open-jaw" configuration of many retrieval flights. Helicopters are not always based at hospitals. We modeled coverage based on different outbound and inbound flights. Areally referenced population data were obtained from the Scottish Government. RESULTS: The current helicopter network configuration provides 94.2% population coverage and 59.0% area coverage. The addition of a fourth helicopter would marginally increase population coverage to 94.4% and area coverage to 59.1%. However, when considering only physician-manned aircraft, the current configuration provides only 71.7% population coverage and 29.4% area coverage, which would be increased to 91.1% and 51.2%, respectively, with a second aircraft. CONCLUSIONS: Scotland's current helicopter network configuration provides good population coverage for retrievals to major trauma centers, which would only be increased minimally by the addition of a fourth aircraft in the North East. The coverage provided by the single physician-staffed aircraft is more limited, however, and would be increased considerably by a second physician-staffed aircraft in the North East. Elliptical isochrones provide a useful means of modeling "open-jaw" retrieval missions and provide a more realistic estimate of coverage. LEVEL OF EVIDENCE: Epidemiological study, level IV; therapeutic study, level IV.

Connexin 43 in the development and progression of breast cancer: What's the connection? (Review).

Connexin 43 is a prominent gap junction protein within normal human breast tissue. Thus far, there have been a number of research studies performed to determine the function of connexin 43 in breast tumor formation and progression. Within primary tumors, research suggests that the level of connexin 43 expression in breast tumors is altered when compared to normal human breast tissue. While some reports indicate that connexin 43 levels decrease, other evidence suggests that connexin 43 levels are increased and protein localization shifts from the plasma membrane to the cytoplasm. In either case, the prevailing theory is that breast tumor cells have reduced gap junction intercellular communication within primary tumors. The current consensus appears to be that the loss of connexin 43 gap junction intercellular communication is an early event in malignancy, with the possibility of gap junction restoration in the event of metastasis. However, additional evidence is needed to support the latter claim. The purpose of this report is to review the connexin 43 literature that describes studies using human tissue samples, in order to evaluate the function of connexin 43 protein in normal human breast tissue as well as the role of connexin 43 in human breast tumor formation and metastatic progression.

Dysregulated connexin 43 in HER2-positive drug resistant breast cancer cells enhances proliferation and migration.

Connexin 43 (Cx43) is a gap junction protein whose function in the development of breast cancer and in breast cancer progression remains unclear. Evidence suggests that Cx43 (GJA1) mRNA and protein expression is altered in breast tumors. However, reports indicate both increased and decreased Cx43 levels in human breast cancer samples. Studies also suggest that loss of Cx43 regulated gap junction intercellular communication is a common feature of breast malignancies that potentially correlates with histological stage. Further evidence suggests that Cx43 (GJA1) mRNA expression is negatively correlated with HER2 positivity but a relationship between Cx43 and HER2 in breast cancer is not well defined. Therefore, in this study, we sought to evaluate the relationship between Cx43 activity, HER2, and drug resistance. Using HER2+ breast cancer cell lines that are sensitive or resistant to HER2 inhibitor, we evaluated Cx43 gap junction function. We found that Cx43 gap junction activity is completely lost in drug resistant HER2-positive (HER2+) breast cancer cells, whereas Cx43 gap junction activity can be restored by Cx43 overexpression in drug sensitive HER2+ cells. Moreover, the dysregulation of Cx43 resulted in increased tumorigenic and migratory capacity of the HER2+ drug resistant breast cancer cells.

The analgesic efficacy of intravenous lidocaine infusion after laparoscopic fundoplication: a prospective, randomized, double-blind, placebo-controlled trial.

This study aimed to determine if intravenous lidocaine infusion reduces postoperative pain intensity following laparoscopic fundoplication surgery and to also validate the safety of intravenous lidocaine at the dose tested. This was an equally randomized, double-blind, placebo-controlled, parallel-group, single center trial. Adult patients undergoing laparoscopic fundoplication were recruited. The intervention group received 1 mg/kg intravenous lidocaine bolus prior to induction of anesthesia, then an intravenous infusion at 2 mg/kg/h for 24 hours. The primary outcome was pain, measured using a numeric rating scale for 30 hours postoperatively. Secondary outcomes were nausea and vomiting, opioid requirements, adverse events, serum lidocaine concentration, and length of hospital stay. The study was terminated after an interim analysis of 24 patients showed evidence of futility. There was no difference in postoperative pain scores (lidocaine versus control, mean ± standard deviation) at rest (2.0 ± 2.7 vs 2.1 ± 2.4, P=0.286) or with movement (2.0 ± 2.6 vs 2.6 ± 2.7, P=0.487). Three adverse events occurred in the lidocaine group (25% of patients). Intravenous lidocaine did not provide clinically significant analgesia to patients undergoing laparoscopic fundoplication. The serum lidocaine concentration of patients who experienced adverse events were within the therapeutic range. This trial cannot confirm the safety of intravenous lidocaine at the dose tested.

Encouraging acceptance of ambivalence using the expressive writing paradigm.

OBJECTIVES: Ambivalence is regarded as a key target for psychotherapeutic change. This study aimed to examine the effectiveness of a brief expressive writing intervention for reducing distress about goal ambivalence. DESIGN: A sample of 40 undergraduate students were randomly allocated to an experimental 'expressive writing' condition or a control condition. METHOD: Participants rated their ambivalence about the 10 most important goals they were currently pursuing and rated how distressing they found these feelings of ambivalence. Participants then completed three short expressive writing sessions on consecutive days. Participants in the experimental condition participants wrote about their deepest thoughts and feelings relating to their ambivalence, and participants in the control condition wrote about how they had spent their time that day or week. RESULTS: When controlling for baseline distress about ambivalence, there was a significant effect of writing condition on distress about ambivalence at follow-up; individuals who wrote about their ambivalence experienced a significant reduction in their level of distress about ambivalence. CONCLUSION: It was concluded that expressive writing might represent an analogue of therapeutic approaches to encourage acceptance of ambivalence.