Pain: evolutionary background and primary stimulus.
The evolution of aerobic organisms required the development of oxygen sensors so the organism could avoid anoxic environments. In man these oxygen sensors are known as pain receptors. The skin pain receptor includes the epidermis and the dermal papilla with its capillary and terminal nerve. A pain stimulus such as a pin prick occludes blood flow into the papilla. The epidermal cells consume enough residual oxygen to produce a fall in oxygen tension at the nerve ending sufficient to cause the nerve to fire. The maximum time required for the oxygen drop is 0.04 seconds.


Correspondence between middle frequency auditory loss in vivo and outer hair cell shortening in vitro.
The aromatic hydrocarbon, toluene, has been reported to disrupt auditory system function both in occupational epidemiological and in laboratory animal investigations. This agent, along with several other organic solvents, impairs hearing preferentially at middle frequencies - a finding that distinguishes these agents from the traditional high frequency impairment observed with ototoxic drugs such as aminoglycoside antibiotics and cisplatin. Prior investigations performed in vivo have identified the outer hair cell as a probable target for toluene exposure. The purpose of this investigation was to determine directly whether outer hair cells isolated from the guinea pig cochlea show morphological alterations consistent with the toxic response seen in physiological studies with toluene exposure. The effect of toluene superfusion on outer hair cell shortening was assessed for cells harvested from different locations within the cochlea. Control studies included assessment of cell shortening among outer hair cells exposed to trimethyltin and cells exposed to benzene. Trimethyltin disrupts high frequency hearing preferentially and benzene does not produce hearing loss in vivo. Toluene at a concentration of 100 microM produced a marked shortening of outer hair cells although the effect was significantly greater among cells isolated from the apical half of the cochlea than from the basal half of the cochlea. By contrast, trimethyltin at the same concentration produced a preferential shortening among outer hair cells from the base of the cochlea. Benzene (100 microM) did not disrupt outer hair cell length of cells harvested from the apex. The results indicate that intrinsic features of outer hair cells contribute significantly to the site of ototoxic impairment observed in vivo for toluene.


Medical treatment of prolactinomas.
Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas.


Anti-platelet effects of clopidogrel in rat middle cerebral artery thrombosis model.
We have developed a model whereby the middle cerebral artery (MCA) in an experimental animal can be occluded by photochemical reaction between rose bengal and green light which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. Using this model, we investigated the effect of clopidogrel, an analogue of ticlopidine which is a potent inhibitor of adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oral clopidogrel (3-10mg/kg) inhibited ex-vivo platelet aggregation induced by ADP, thrombin or the thromboxane A2 mimetic, and U46619, when platelets had been primed with low concentration of phorbol myristate acetate. At these doses, clopidogrel significantly (P < 0.001) prolonged the time to produce thrombotic occlusion of the MCA and induced a significant (P < 0.001) reduction in the size of ischaemic cerebral damage examined 24 hours after photochemical reaction. The results suggest that ADP has a key role in the thrombotic occlusion of the MCA in this model. Clopidogrel may be beneficial in the prevention of arterial thrombosis.


Rotavirus infection causes mesenteric lymph node hypertrophy independently of type I interferon or TNF-α in mice.
Lymphoid organ hypertrophy is a characteristic feature of acute infection and is considered to enable efficient induction of adaptive immune responses. Accordingly, oral infection with rotavirus induced a robust increase in cellularity in the mesenteric LNs, whose kinetics correlated with viral load and was caused by halted lymphocyte egress and increased recruitment of cells without altered cellular proliferation. Lymphocyte sequestration and mesenteric LN hypertrophy were independent of type 1 IFN receptor signaling or the continuous presence of TNF-α. Our results support previous findings that adaptive immunity toward rotavirus is initiated primarily in the mesenteric LNs and show that type I IFN or TNF-α are not required to coordinate the events involved in the LN response.


Serum alanine aminotransferase activity in obese children.
To confirm the significance of the serum alanine aminotransferase (ALT) test for the diagnosis of fatty liver and to clarify the relationship between serum ALT activity and the duration of obesity, we analysed 310 obese young school children (195M, 115F), who were classified into three duration groups (1-3 y, 4-6 y, 7 + y), three age groups (6-7 y, 8-9 y, 10-11 y), and four obesity groups (weight excess: mild, 20-29%; moderate, 30-39%; severe, 40-49%; very severe, 50%). Seventy-seven patients with abnormal ALT test, > 30 IU/l, and 27 patients with normal ALT test were examined by ultrasound study to identify the fatty-fibrotic pattern of the liver. Abnormal results of the serum ALT test were found in 24% of all patients. The fatty-fibrotic pattern was identified in 64/77 (83%) patients with abnormal ALT test and in 5/27 (18%) patients with normal ALT test. The serum ALT test has a sensitivity of 0.92 for detecting the fatty-fibrotic pattern proven by ultrasound study. Frequencies of cases with abnormal serum ALT levels increased with the duration of obesity. In the shortest duration group, however, the frequencies of abnormal results in serum ALT test did not increase with advanced ages or the grades of obesity. In conclusion, the present study confirmed the usefulness of the serum ALT test for screening fatty liver, and showed that a longer duration of obesity is generally associated with the occurrence of fatty liver in a paediatric obese population. In young patients with mild obesity or a short duration of obesity, however, fatty liver or fatty fibrosis may develop. Early intervention should be made in the case of obese children.


Patient reported outcomes after definitive open tibial fracture management.
Open tibial fractures are often life-changing injuries and patient outcomes remain poor despite the introduction of national management guidelines. The longer-term impact to the patient can be considerable but this is often overlooked in the literature. This study aims to establish the functional, physical, and psychosocial impact of sustaining an open tibial fracture. We reviewed 69 consecutive Gustilo-Anderson grade IIIB and IIIC open tibial fractures that presented to our Major Trauma Centre (MTC) between September 2012 and April 2018. Each participant was interviewed and sent patient-reported outcome questionnaires, a minimum of 12 months following injury. Our primary outcome was the Lower Extremity Functional Scale (LEFS). Secondary outcomes included the Short-Form 36 Healthy Survey (SF-36), Sickness Impact Profile 128 (SIP) and return to occupation. Subgroups were analysed according to age, Injury Severity Score (ISS) and limb amputation. The mean follow up was 43 months. 96% were grade IIIB and 4% grade IIIC. The response rate for our study was 72%. The mean LEFS was 42 (IQR 21.5-58.5). All total and sub-domain scores within both the SF-36 and SIP questionnaires were reduced when compared to normative population data. Only 48% of patients returned to full time employment. Subgroup analysis revealed significantly reduced LEFS, SIP and SF-36 subdomain scores for those with a presenting ISS >14 and those undergoing limb amputation. Patients are at significant risk of longer-term functional, physical and psychosocial harm after suffering an open tibial fracture. Those sustaining major polytrauma or amputation demonstrated to have the greatest risk of poor outcome. Early identification of these individuals likely to suffer most from their injury would help direct appropriate resources to those with greatest need at the earliest opportunity.


Community participation in AIDS vaccine trials: empowerment or science?
For future AIDS vaccines to be successfully tested and implemented, extensive participation in vaccine trials will be necessary. Central to the challenges associated with such participation is concern for protection of participant wellbeing. This short report examines the tension that is sometimes found between the pragmatic need for recruitment into trials, and a more general social good concerning community participation in health. Community empowerment and trial participation are sometimes assumed to go hand in hand, but are potentially contradictory. Recognizing the possible disjunction between empowerment and trial participation allows for clearer discussion of and planning for ethical, scientifically valid trials.


A population-based paediatric Covid-19 vaccination progress and outcomes: The Malta case.
Covid-19 is still pandemic with population vaccination, including among children, remaining the mainstay for hastening the exit from the pandemic. The article provides an insight in Malta's national paediatric vaccination modus operandi, vaccination uptake, and epidemiological trends while exploring geographical social inequalities among the ≤ 15 years cohort up till end of August 2022. The Vaccination Coordination Unit in Malta's only regional hospital provided an account of the strategic roll-out along with anonymised cumulative vaccination doses by age band and district. Descriptive and multivariant logistic regression analyses were performed. By mid-August 2022, 44.18% of the under 15's population had received at least 1 vaccine dose. A bi-directional relationship was observed between increased cumulative vaccination and reported Covid-19 cases until early 2022. Central vaccination hubs were set up with invitation letters and SMSs sent to parents. Children residing in the Southern Harbour district (OR: 0.42, P < 0.01) had the highest full vaccination uptake (46.66%) as opposed to the Gozo district (lowest at 27.23%; OR: 0.3, P = 0.01). Successful paediatric vaccination is not only dependent on easily accessible vaccination but also on vaccine effectiveness against variants, as well as population characteristics, with potential geographical social inequalities hindering uptake.


Voluntary exercise and experimental mammary cancer.
The results of these studies indicate that voluntary activity suppresses the development of chemically and virally induced primary mammary tumors in rats and mice fed high-fat diets. These diets were chosen to mimic the current U.S. fat consumption of approximately 40% of calories as fat. It remains to be seen if activity exerts a similar suppressive effect on animals fed their customary low-fat diet (10% calories as fat). In general, the activity profiles of the female Fischer F-344 and Sprague-Dawley rat and the C3H/o mu j mouse exhibited a similar pattern with an early peak followed by a gradual plateau over time. The effects of activity on body fat composition showed a trend toward a decreased percent of body fat when compared to sedentary animals but a statistically significant decrease was found only in the F-344 female rat. In the DMBA model, carcinogen dose did alter outcome parameters. For example, time to first tumor was extended under low- but not high-DMBA conditions, and, conversely, tumor multiplicity was significantly decreased in the high- but not low-DMBA group. In the NMU model, an inverse association was found between the amount of activity and tumor incidence. A similar association was not found with the DMBA model. The reason for this is uncertain, but further analysis in terms of other parameters such as total tumor number may shed more light on this discrepancy. The suppressive effect of activity on the MMTV-induced mouse mammary tumor is of particular interest since it raises the possibility that activity may exert effects on the process of provirus insertion, and/or oncogene activation--an area of great potential promise in cancer prevention. Activity appeared to enhance the volume and to a lesser degree the number of metastatic foci in the lungs of F-344 retired breeders under high-fat but not medium-fat conditions. In addition, the most active animals in the high-fat group exhibited the greatest volume of metastases. These results, together with those in the NMU model, point to the critical importance of the quantity of voluntary activity an animal engages in and its relation to both primary and secondary cancer prevention. They imply that beyond a certain point of either frequency or intensity, the beneficial effect of exercise may be nullified by competing deleterious effects. The metastases study has also brought to light the importance of dietary fat as a potential intervening variable.(ABSTRACT TRUNCATED AT 400 WORDS)


In vitro activity of cefoperazone/sulbactam and other antimicrobials against anaerobic bacteria.
Sulbactam inhibits the hydrolytic activity of several, clinically important beta-lactamases including those produced by anaerobic bacteria. This study was undertaken to determine the effect of sulbactam on the activity of cefoperazone against 250 anaerobic bacteria including 174 isolates belonging to the Bacteroides fragilis group and to compare the activity of cefoperazone/sulbactam with other antimicrobial agents. beta-lactamase activity was detected in 98% of the isolates of the Bacteroides fragilis group but not in the other species evaluated. Antagonistic activity between cefoperazone and sulbactam was not observed with any of the species. Forty-two percent of the isolates belonging to the B. fragilis group were resistant to cefoperazone. Ninety-four percent of these were converted to either the susceptible or moderately susceptible range upon the addition of sulbactam. Sixty-seven percent were susceptible to the combination cefoperazone/sulbactam and 27% were moderately susceptible. Overall, metronidazole and chloramphenicol were the most active antimicrobials. Significant differences in the antimicrobial susceptibility patterns of members of the B. fragilis group were observed. Sulbactam demonstrated some intrinsic activity against all of the species tested.


Substantial Reduction in Particulate Matter Air Pollution across Europe during 2006-2019: A Spatiotemporal Modeling Analysis.
Air pollution poses the largest environmental health risk in Europe. Particulate matter (PM) concentrations are the most harmful pollutants representing the main air quality indicator in the Sustainable Development Goals (SDGs). The air quality surveillance in Europe is based on a monitoring network that is too coarse for a comprehensive evaluation of the air pollution burden. We link raw pollutant data with remotely sensed products using Bayesian geostatistical models and for the first time estimate pan-European near-surface concentrations of both fine (PM2.5) and coarse (PM10) particles at 1 km2 spatial resolution during 2006-2019. We evaluate the compliance with the air quality thresholds set by the World Health Organization (WHO) and the European Union (EU) and assess country-wise trends. The results show that during the last 14 years, PM10 and PM2.5 concentrations declined by 36.5% (95% credible interval: 30.3, 41.9%) and 39.1% (26.6, 50.5%), respectively. The number of people exposed to PM10 levels above the WHO thresholds decreased from 78.3% (52.6, 91.8%) in 2006 to 28.4% (16.2, 43.7%) in 2019; for PM2.5, the decrease was smaller: from 91.0% (61.3, 99.1%) exposed in 2006 to 53.6% (33.5, 76.3%) in 2019. Although there is a clear improvement in the overall picture, stricter measures are needed to ensure compliance with the WHO guidelines.


Effects of nanodiamonds of explosive synthesis on the skin of experimental animals locally exposed to cobalt and chrome ions.
Experiments in vivo demonstrated the protective effect of modified nanodiamonds on guinea pig skin after local exposure cobalt ions, but not chrome ions. The observed differences are determined by different adsorption of these ions by nanodiamonds: in vitro experiments showed that nanodiamonds adsorbed cobalt ions, but not chrome ions from water solutions. The perspectives of using modified nanodiamonds as a new adsorbent for prevention of allergic contact dermatitis induced by ions of bivalent metals are discussed.


Evaluation of the toxic potential of the aqueous extract from Mangifera indica Linn. (Anacardiaceae) in rats submitted to experimental models of acute and subacute oral toxicity.
The population has traditionally used the Mangifera indica plant leaves to treat diseases such as Diabetes Mellitus and alleviate signs and symptoms such as inflammation, diarrhea, and dysentery. In a previous study, we demonstrated that the flavonoids present in the aqueous extract from M. indica leaves (EAMI) exhibited a potent hypoglycemic effect in diabetic rats, promoting the widespread use of the plant by the population and highlighting the importance of investigating its oral toxicity. The present study aimed to assess the toxic potential of EAMI in rats submitted to experimental models of acute and subacute (short-term) oral toxicity. For the acute toxicity test, female Wistar rats received a single oral dose of 2000 mg/kg body weight of EAMI and were observed for 14 days. In the short-term toxicity test, male and female Wistar rats received repeated oral EAMI doses of 125, 250, 500 or 1000 mg/kg body weight and observed for 28 days. The phytochemical analysis of EAMI demonstrated that the extract has high levels of flavonoids. No animals died in the acute toxicity test, and no clinical changes were observed that show signs of toxicity in the animals. There was no significant change in the weight of the organs of the animals submitted to tests with the EAMI, suggesting that LD50 is greater than 2000 mg/kg. In the conditions and doses tested in the short-term toxicity experiments, the treatment did not produce significant changes in the physiological, biochemical, hematological, and histopathological parameters in the animals evaluated. Our study demonstrated that high doses of EAMI administered acutely, as well as all doses evaluated in the short-term oral toxicity model, should be considered safe during traditional therapeutic use.


Asymptomatic heart valve dysfunction in healthy middle-aged companion dogs and its implications for cardiac aging.
Heart disease is the leading cause of death in the USA, accounting for about one in every four deaths. Age is the greatest risk factor for heart disease in both people and dogs; however, heart disease is generally not considered as a major cause of morbidity or mortality in dogs. As part of the preliminary selection process for a veterinary clinical trial, 40 companion dogs with no history of cardiac pathology that were at least 6 years old and weighed at least 18 kg underwent a cardiac screening using Doppler echocardiography. Eleven dogs from this cohort were diagnosed with valvular regurgitation by echocardiography, and seven of these cases were of sufficient severity to warrant exclusion from the clinical trial. In only one case was a heart murmur detected by auscultation. Serum alkaline phosphatase levels were significantly higher in the dogs with moderate to severe valvular regurgitation compared to the rest of the cohort. These observations suggest that asymptomatic degenerative valvular disease detectable by echocardiography, but not by a standard veterinary exam including auscultation, may be present in a significant fraction of middle-aged companion dogs, indicating a previously underappreciated similarity between human and canine aging. Further, these data suggest that companion dogs may be a particularly useful animal model for understanding mechanisms of age-related degenerative valve disease and for developing and testing interventions to ameliorate cardiac disease. Future studies should address whether dogs with asymptomatic valve disease are at higher risk for subsequent morbidity or early death.


Influence of formulation composition and process on the characteristics and in vitro release from PLGA-based sustained release injectables.
Understanding and controlling the in vitro release behavior of a formulation is a first step toward rationalized selection of a solubility enhancing formulation strategy with a desired release profile in vivo. Therefore six model formulations, representing three different formulation strategies, were physicochemically analyzed and their in vitro release was determined. Solid dispersions based on a PLGA/PVP matrix were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. Depending on composition and manufacturing method, formulations varied in particle size, porosity, phase behavior, surface coverage and physical state of the API. This resulted in observed differences in their in vitro release profile. For the various formulation strategies tested both a porous PLGA-based formulation and PLGA/PVP-based formulations, resulted in vitro in sustained release of the poorly soluble API with over 50% of drug released after 24h. For PLGA-based formulations the porosity was identified as a critical parameter influencing in vitro drug release. For the PLGA/PVP-based formulations the release rate can be tailored by the amount of PLGA present. Particle size reduction resulted in immediate total drug release.


Morphological evaluation of the cerebral blood vessels in the late gestation fetal sheep following hypoxia in utero.
Hypoxia can significantly contribute to the development of permanent brain injury in the term neonate; however the response of cerebral blood vessels is not well understood. This study aimed to quantitatively measure vascular density and morphology using laminin immunohistochemistry as a marker of blood vessels, and determine the effects of a single, severe bout of hypoxia (umbilical cord occlusion, UCO) late in gestation on the developing cerebrovasculature in fetal sheep. At 124-126 days gestation singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. A 10 min UCO or sham UCO (n=5) occurred at 132 days gestation. Fetal brains were collected at 24 h (n=5) or 48 h (n=4) after UCO for vascular density and morphology analysis of laminin immunohistochemistry. 48 h following a single, brief bout of severe hypoxia late in gestation decreased vascular density was seen in the caudate nucleus and no changes in vascular morphology occurred. However closer analysis revealed a significant shift in the frequency of smaller (≤10 μm) to larger (≤100 μm) perimeter blood vessels in periventricular and subcortical white matter. Close examination of the frequency distribution of vascular perimeter highlights that alterations in vascular morphology persist in the near term fetal brain for up to 48 h following a brief (10 min) hypoxia in white but not gray matter. These findings suggest that the near term brain may still be vulnerable to white matter injury following in utero hypoxia.


Effect of diazepam and phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol in rats.
Diazepam, a well known tranquilizer, and ethinyl estradiol have frequently been prescribed together in rape cases. These two drugs were reported to possess an opposite action on uterine motility. Phenobarbital, a typical enzyme inducer, has been prescribed together with ethinyl estradiol in some cases as a sedative-hypnotic. The present study was, therefore, designed to investigate the possible interferences of diazepam or phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol (4 micrograms/kg/day) in rats. All tested doses of diazepam (1, 2 and 4 mg/kg/day) or phenobarbital sodium (30 and 60 mg/kg/day) appear to have no effect on the efficacy of ethinyl estradiol when either of them was administered from D3 to D5 or from D1 to D5 of pregnancy. In addition, neither diazepam nor phenobarbital sodium at the highest doses used showed an effect on pregnancy.


Outcomes of hypoplastic left heart syndrome in low-birth-weight patients.
The objective of this study was to assess outcomes of hypoplastic left heart syndrome (HLHS) patients weighing ≤ 2.5 kg throughout staged palliation. We performed a single-center retrospective review. Abstracted data included gestational age, birth weight, presence of noncardiac anomalies, and survival through Fontan. Fifty-two patients met inclusion criteria, with a median birth weight of 2.14 kg and gestational age of 36 weeks. Five patients received comfort care only. Of 47 patients who underwent initial surgical palliation, 51% survived to initial hospital discharge. Birth weight and gestational age (GA) were similar between survivors and nonsurvivors. Compared with survivors, risk factors for death prior to initial hospital discharge were as follows: small for GA (P = 0.005), noncardiac anomalies (P = 0.04), need for post-perative extracorporeal membrane oxygenation (P = 0.0004), and conversion from initial palliation to Sano shunt (n = 5, no survivors). Operative survival following Stage 2 palliation was 91% (21/23) and 94% after Fontan (17/18). Overall survival for palliated patients from birth through Fontan was 36%. Low-birth-weight neonates with HLHS have poor overall survival through the Fontan operation, with highest mortality following Stage 1 palliation. Being small for GA and the presence of noncardiac anomalies are important preoperative risk factors for early mortality.


Influence of aging and poly IC treatment on xenobiotic metabolism in mice.
Cytochrome P-450-dependent and independent metabolism of xenobiotics in the liver of C57BL/10ScSn male mice was investigated in relation to age and the age-related differences in response to treatment with polyriboinosinic-polyribocytidylic acid (poly IC), an interferon inducing agent. Young (3 months), middle-aged (15 months) and old (27 months) animals were studied. Mean survival time of males of this strain is 30-33 months. Age-related changes in the metabolism of xenobiotics included significant decreases between middle and old age in activities of the microsomal P-450-dependent mixed function oxidases (MFO), aryl hydrocarbon hydroxylase (AHH) and p-nitroanisole (p-NA) O-demethylase, but not 7-ethoxycoumarin (7-Ec) O-deethylase. Analysis of P-450-independent enzymes revealed a significant decrease in the epoxide hydrolase activity in the microsomes and cytosol from old compared to middle-aged or young mice. Glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was lower in cytosols of middle-aged and old than young mice. Carboxylesterase activity was not altered by age. Hepatic microsomal protein content was significantly higher in middle-aged and old than in young mice. Intraperitoneal treatment with a single dose of 5 mg/kg poly IC 24 hours before sacrifice resulted, for mice of all age groups, in a marked inhibition of activities of all 3 microsomal cytochrome P-450-dependent enzymes, without any changes in activities of the P-450-independent enzymes. The inhibition of AHH by poly IC was much higher in old and middle-aged than in young mice, averaging 87.1%, 74.5%, and 41.9%, respectively, in the 3 age groups. Poly IC treatment increased lipid peroxidation in liver homogenates of all groups of mice. Body and liver weights were not altered in animals of the 3 age groups by poly IC treatment, but hepatic microsomal protein contents were significantly decreased.


[The effect of pesticide acetamiprid on biochemical markers in tissues of fresh water bivalve mussels Anodonta cygnea L. (Unionidae)].
The effects of ecological real concentration of pesticide "Mospilan" (active substance - acetamiprid) on the status of oxidative stress biomarkers, neurotoxicity and metallothioneins' (MTs) characteristics of freshwater bivalve mussels Anodonta cygnea were investigated. The prooxidative changes (decrease of superoxide dismutase activity, reduced glutathione content, increase of content of lipid and proteins peroxidation products) and decrease of the MTs content in gills and especially in digestive gland in the experimental group were reflected, whereas acetylcholinesterase activity was not changed. The effect of acetamiprid induces the appearance of additional chromatographic MTs form.


Case report of Brunner's gland hyperplasia: A rare "mimic" of malignant pathology.
Brunner's gland hyperplasia is a rare, benign lesion of the duodenum. The symptomology can range from asymptomatic (as an incidental finding on endoscopy) to gastrointestinal obstruction or haemorrhage. We report a case of a 60-year-old man presenting with post-prandial vomiting and weight loss. Inpatient evaluation led to the likely diagnosis of a duodenal malignancy for which the patient underwent a laparotomy and proximal duodenectomy. Brunner's gland hyperplasia is a rare, benign condition that can be overtreated due to the difficulty in obtaining an accurate pre-operative diagnosis. The literature has been reviewed to discuss the approach to diagnosis. This case highlights the potential for Brunner's gland hyperplasia mimicking a malignancy.


Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing.
Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.


[Analysis of a blog for gastrointestinal disease in the view point of the big data: a single institutional study].
With the enormous increase in the amount of data, the concept of big data has emerged and this allows us to gain new insights and appreciate its value. However, analysis related to gastrointestinal diseases in the viewpoint of the big data has not been performed yet in Korea. This study analyzed the data of the blog's visitors as a set of big data to investigate questions they did not mention in the clinical situation. We analyzed the blog of a professor whose subspecialty is gastroenterology at Gangnam Severance Hospital. We assessed the changes in the number of visitors, access path of visitors, and the queries from January 2011 to December 2013. A total of 50,084 visitors gained accessed to the blog. An average of 1,535.3 people visited the blog per month and 49.5 people per day. The number of visitors and the cumulative number of registered posts showed a positive correlation. The most utilized access path of visitors to the website was blog.iseverance.com (42.2%), followed by Google (32.8%) and Daum (6.6%). The most searched term by the visitors in the blog was intestinal metaplasia (16.6%), followed by dizziness (8.3%) and gastric submucosal tumor (7.0%). Personal blog can function as a communication route for patients with digestive diseases. The most frequently searched word necessitating explanation and education was 'intestinal metaplasia'. Identifying and analyzing even unstructured data as a set of big data is expected to provide meaningful information.


Vaccine effectiveness of two-dose BNT162b2 against symptomatic and severe COVID-19 among adolescents in Brazil and Scotland over time: a test-negative case-control study.
Little is known about vaccine effectiveness over time among adolescents, especially against the SARS-CoV-2 omicron (B.1.1.529) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. We did test-negative, case-control studies in adolescents aged 12-17 years with COVID-19-related symptoms in Brazil and Scotland. We linked records of SARS-CoV-2 RT-PCR and antigen tests to national vaccination and clinical records. We excluded tests from individuals who did not have symptoms, were vaccinated before the start of the national vaccination programme, received vaccines other than BNT162b2 or a SARS-CoV-2 booster dose of any kind, or had an interval between their first and second dose of fewer than 21 days. Additionally, we excluded negative SARS-CoV-2 tests recorded within 14 days of a previous negative test, negative tests recorded within 7 days after a positive test, any test done within 90 days after a positive test, and tests with missing sex and location information. Cases (SARS-CoV-2 test-positive adolescents) and controls (test-negative adolescents) were drawn from a sample of individuals in whom tests were collected within 10 days of symptom onset. We estimated the adjusted odds ratio and vaccine effectiveness against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil across fortnightly periods. We analysed 503 776 tests from 2 948 538 adolescents in Brazil between Sept 2, 2021, and April 19, 2022, and 127 168 tests from 404 673 adolescents in Scotland between Aug 6, 2021, and April 19, 2022. Vaccine effectiveness peaked at 14-27 days after the second dose in both countries during both waves, and was significantly lower against symptomatic infection during the omicron-dominant period in Brazil (64·7% [95% CI 63·0-66·3]) and in Scotland (82·6% [80·6-84·5]), than it was in the delta-dominant period (80·7% [95% CI 77·8-83·3] in Brazil and 92·8% [85·7-96·4] in Scotland). Vaccine efficacy started to decline from 27 days after the second dose for both countries, reducing to 5·9% (95% CI 2·2-9·4) in Brazil and 50·6% (42·7-57·4) in Scotland at 98 days or more during the omicron-dominant period. In Brazil, protection against severe disease remained above 80% from 28 days after the second dose and was 82·7% (95% CI 68·8-90·4) at 98 days or more after receiving the second dose. We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in Brazil and Scotland from 27 days after the second dose. However, protection against severe COVID-19 outcomes remained high at 98 days or more after the second dose in the omicron-dominant period. Booster doses for adolescents need to be considered. UK Research and Innovation (Medical Research Council), Scottish Government, Health Data Research UK BREATHE Hub, Fiocruz, Fazer o Bem Faz Bem programme, Brazilian National Research Council, and Wellcome Trust. For the Portuguese translation of the abstract see Supplementary Materials section.


Clinical and morphological investigations on ependymomas and their tissue cultures.
A morphological investigation was carried out on 56 ependymomas cultivated in vitro as short-term cultures in roller tubes. The tumours had been histologically classified as cellular and fibrillary ependymomas, subependymomas, myxopapillary and malignant ependymomas (Table 1). A very good growth was detected in 32 cases, most of them being cellular and malignant ependymomas (Table 2). The prevailing growth pattern was epithelial in type, i.e. proliferating cells forming a carpet. In some cases, in the first stages of growth elongated bipolar cells did appear, but they evolved later as flattened epithelial elements. In four cases, a mixed proliferation of piloid astrocytes and ependymal cells was seen; these tumours were regarded as mixed gliomas. In 46 cases an exact evaluation of the history was possible. Although no correlation could be found between histology and survival time (Table 4), the longest survival was observed in spinal tumours (Table 3). Tumours in children had a slightly worse prognosis in comparison with adults (Table 5). A radical removal of the tumour was generally followed by a longer survival time (Table 6), although the operative procedure employed did not seem to influence the development of recurrences (Table 7).


Acute toxicity of pyrazolones.
Pyrazolone intoxication accounts for most (52 percent) mild analgesic poisonings in West Germany. Severe and fatal intoxication with pyrazolones is, however, rare. In the German literature, only 50 cases have been described in the past 62 years; 80 to 90 percent of these were caused by aminopyrine, which was withdrawn from the West German market in 1978 and replaced by propyphenazone. Up to now, no fatal poisoning with propyphenazone has been reported. However, the signs and symptoms of severe intoxication are similar for both propyphenazone and aminopyrine. The acute toxicity of dipyrone is slightly lower than that of propyphenazone, whereas phenylbutazone and oxyphenbutazone clearly cause less severe reactions. Characteristic symptoms include impaired consciousness progressing to coma, and convulsions. In addition, arrhythmia and cardiogenic shock may occur. Severe aminopyrine intoxication may also be complicated by sudden apnea. Liver damage may develop after a latent period of about 24 hours, especially after phenylbutazone and oxyphenbutazone poisoning. Therapy involves supportive measures as well as gastric emptying by emesis or lavage, installation of medical charcoal, and induction of diarrhea or gut lavage. Although exact clinicotoxicologic data on hemoperfusion are not available as yet, distribution volumes, plasma half-lives, and endogenous plasma clearances as well as results of in vitro trials all suggest the efficacy of this procedure. Hemoperfusion with uncoated amberlite XAD-4 resin is, therefore, recommended for patients with severe pyrazolone intoxication.


Loss of TREM2 facilitates tau accumulation, spreading, and brain atrophy, but only in the presence of amyloid pathology.
TREM2 variants increase the risk for Alzheimer's disease. In this issue of Neuron, Lee et al. demonstrate that TREM2-dependent microglial functions prevent accumulation and spreading of tau, but only in the presence of amyloid pathology. This provides additional fuel for the amyloid cascade hypothesis and supports a protective function of microglia.


Enhancing the phase stability of ceramics under radiation via multilayer engineering.
In metallic systems, increasing the density of interfaces has been shown to be a promising strategy for annealing defects introduced during irradiation. The role of interfaces during irradiation of ceramics is more unclear because of the complex defect energy landscape that exists in these materials. Here, we report the effects of interfaces on radiation-induced phase transformation and chemical composition changes in SiC-Ti3SiC2-TiC x multilayer materials based on combined transmission electron microscopy (TEM) analysis and first-principles calculations. We found that the undesirable phase transformation of Ti3SiC2 is substantially enhanced near the SiC/Ti3SiC2 interface, and it is suppressed near the Ti3SiC2/TiC interface. The results have been explained by ab initio calculations of trends in defect segregation to the above interfaces. Our finding suggests that the phase stability of Ti3SiC2 under irradiation can be improved by adding TiC x , and it demonstrates that, in ceramics, interfaces are not necessarily beneficial to radiation resistance.


Neuroimaging correlates of emotional response-inhibition discriminate between young depressed adults with and without sub-threshold bipolar symptoms (Emotional Response-inhibition in Young Depressed Adults).
Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-). This study included 118 medication-free young adults (15 - 30 yrs.): 20 BDD, 28 MDD+, 41 MDD- and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were conducted. MDD- group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern. Results also need to be tested in a different independent dataset. Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects.


Characterization of visna virus envelope neuraminic acid.
Visna virus particles inhibit influenza virus hemagglutination in an assay for neuraminic acid-containing viruses. Pretreatment of visna virus with neuraminidase abolished hemagglutination inhibition activity but did not significantly affect attachment, infectivity, or virus-induced cell fusion in sheep choroid plexus cell monolayers.


A national intervention to support frail older adults in primary care: a protocol for an adapted implementation framework.
Older Canadians are high users of health care services, however the health care system is not well-designed to meet the complex needs of many older adults. Older persons often look to their primary care practitioners to assess their needs and coordinate their care. The intervention seeks to improve primary care for older persons living with frailty and will be implemented in six primary care clinics in three Canadian provinces. Presently, more than 1.6 million older Canadians are living with frailty, and this is projected to increase to 2.5 million within a decade (Canadian Frailty Network, Frailty Matters, 2020). The model will include frailty screening, an online portal to expedite referrals and improve coordination with community services, and several tools and techniques to support patient and family engagement and shared decision-making. Our project is guided by the Consolidated Framework for Implementation Research (CFIR) (Damschroder LJ, et al. Implement Scil, 4, 50, 2009). As others have done, we adapted the CFIR for our work. Our adapted framework combines elements of the socio-ecological model, key concepts from the CFIR, and elements from other implementation science frameworks. Nested within a broader mixed-method implementation study, the focus of this paper is to outline our guiding conceptual framework and qualitative methods protocol. We will use the adapted CFIR framework to inform the data we collect and our analytic approach. Our work is divided into three phases: (1) baseline assessment of 'usual care'; (2) tailoring and implementing a new primary care model; and (3) evaluation. In each of these phases we will engage in qualitative data collection, including clinical observations, focus groups, in-depth interviews and extensive field notes. At each site we will collect data with health care providers, key informants (e.g., executive directors), and rostered patients ≥ 70 years. We will engage in team-based analysis across multiple sites, three provinces and two languages through regular telephone conferences, a comprehensive analysis codebook, leadership from our Qualitative Working Group and a collective appreciation that "science is a team sport" (Clinical Orthopaedics and Related Research 471, 701-702, 2013). Outcomes of this research may be used by other research teams who chose to adapt the CFIR framework to reflect the unique contexts of their work, and clinicians seeking to implement our model, or other models of care for frail older patients in primary care. U.S. National Library of Medicine, NCT03442426 . Registered 22 February 2018- Retrospectively registered.


Performance characteristics and comparison of two immunochemical and two guaiac fecal occult blood screening tests for colorectal neoplasia.
A new immunochemical test for stool Hb, FlexSure OBT, was compared with the immunochemical HemeSelect and guaiac Hemoccult II and Hemoccult SENSA tests. Blinded development of test cards smeared with stools having added human blood showed better analytical sensitivity of FlexSure OBT (0.2 ml blood/100 g feces), than Hemoccult SENSA (> or =0.5 ml) or Hemoccult II (> or =1.0 ml). All four stool tests were prepared by 403 subjects having endoscopic examinations. The guaiac tests and FlexSure OBT were easy to prepare and develop. The positivity rate of Hemoccult SENSA was 8.7%, Hemoccult II 6%, FlexSure OBT 4.2%, and HemeSelect 3.4%. In this mainly asymptomatic (97%) population, 98% were free of clinically significant neoplasia (five had cancers, three had adenomas > or =1.0 cm). Sensitivity for cancers or adenomas > or =1.0 cm was similar for all tests (62.5-86%, NS) and Hemoccult SENSA had the lowest specificity (92% vs 95-98%, P < 0.05); but both Hemoccult II and Hemoccult SENSA had significantly lower predictive positive values (21% and 14%) than either FlexSure OBT (29%) or HemeSelect (50%) (P < 0.05). If both Hemoccult SENSA and FlexSure OBT were positive in the same subjects (1.7%), sensitivity for cancer or adenomas > or =1.0 cm (50%) was not significantly better than guaiac tests, but specificity (99.2%) and predictive positive (57%) values were improved (P < 0.05). In this population, guaiac tests were as sensitive as immunochemical tests for clinically significant colorectal neoplasia, but with significantly lower predictive positive values. A combination of a sensitive guaiac test (Hemoccult SENSA) and a specific confirmatory test for human Hb (FlexSure OBT) provided high specificity, comparable to HemeSelect.


Analyzing chromosome condensation in yeast by second-harmonic generation microscopy.
Condensation is a fundamental property of mitotic chromosomes in eukaryotic cells. However, analyzing chromosome condensation in yeast is a challenging task while existing methods have notable weaknesses. Second-harmonic generation (SHG) microscopy is a label-free, advanced imaging technique for measuring the surface curve of isotropic molecules such as chromatin in live cells. We applied this method to detect changes in chromatin organization throughout the cell cycle in live yeast cells. We showed that SHG microscopy can be used to identify changes in chromatin organization throughout the cell cycle and in response to inactivation of the SMC complexes, cohesin and condensin. Implementation of this method will improve our ability to analyze chromatin structure in protozoa and will enhance our understanding of chromatin organization in eukaryotic cells.


Fatty acids and fatty alcohols of wax esters in the orange roughy: specific textures of minor polyunsaturated and branched-chain components.
Open-tubular gas chromatography was carried out on fatty acids and alcohols obtained from wax esters of the orange roughy, Hoplostethus atlanticus, caught at sea off New Zealand. The major (above 5%) components were 16:1(n-7), 18:1(n-9) and (n-7), 20:1(n-9) and (n-7), and 22:1(n-11, n-13) as fatty acids, and 16:0, 18:0, 18:1(n-9), 20:1(n-9) and (n-7), and 22:1(n-11, n-13) as fatty alcohols. The total percentages of the minor components were 10% in the acids and 26% in the alcohols. The 22:1/20:1 ratio of the fatty alcohols obtained in this study was less than 1.0, although the ratio for the Atlantic orange roughy has been reported as being greater than 1.0. The contents of polyenes were as low as 2.48% in the acids and 0.95% in the alcohols, but their compositions showed some specific features. The percentages of the C16-C22 dienes in the total polyenes were remarkably high, 57.7% of these acids and 53.1% of these alcohols. The most important dienes were 18:2(n-6) in the acids and 20:2(n-6) in the alcohols.


The non-canonical functions of HIF prolyl hydroxylases and their dual roles in cancer.
The hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are dioxygenases using oxygen and 2-oxoglutarate as co-substrates. Under normoxia, PHDs hydroxylate the conserved prolyl residues of HIFα, leading to HIFα degradation. In hypoxia PHDs are inactivated, which results in HIFα accumulation. The accumulated HIFα enters nucleus and initiates gene transcription. Many studies have shown that PHDs have substrates other than HIFα, implying that they have HIF-independent non-canonical functions. Besides modulating protein stability, the PHDs-mediated prolyl hydroxylation affects protein-protein interaction and protein activity for alternative substrates. Increasing evidence indicates that PHDs also have hydroxylase-independent functions. They influence protein stability, enzyme activity, and protein-protein interaction in a hydroxylase-independent manner. These findings highlight the functional diversity and complexity of PHDs. Due to having inhibitory activity on HIFα, PHDs are proposed to act as tumor suppressors. However, research shows that PHDs exert either tumor-promoting or tumor-suppressing features. Here, we try to summarize the current understanding of PHDs hydroxylase-dependent and -independent functions and their roles in cancer.


Deep decarbonization options for the agriculture, forestry, and other land use (AFOLU) sector in Africa: a systematic literature review.
Greenhouse gases (GHG) emanating from agriculture, forestry, and other land use (AFOLU) sector are among top contributors to anthropogenic climate change in Africa and globally. Minimizing AFOLU sector GHG emissions in Africa is notoriously hard because of difficulties in emission estimation, the disperse nature of AFOLU emissions, and the complex links between AFOLU activities and poverty reduction. Yet, there are very few systematic reviews dealing with decarbonization pathways for the AFOLU sector in Africa. This article explores the options for achieving deep decarbonization of AFOLU sector in Africa, through a systematic review. Using the method of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement), 46 studies of interest were selected from the databases of Scopus, Google Scholar, and Web of Science. Four sub-themes were identified from the critical review of the selected studies covering key decarbonization approaches used in AFOLU sector. The literature suggests that while forest management and reforestation reduction of GHG in animal production and climate-smart practices in agriculture hold great promises for AFOLU sector decarbonization in Africa, there appears to be very limited coherent policy in the continent addressing any of these AFOLU sub-sectors.


Relapsing neuropathy due to tetanus toxoid. Report of a case.
A unique case history is presented, of a 42-year-old patient who has suffered three episodes of a demyelinating neuropathy, each of which followed an injection of tetanus toxoid. The clinical features on each occasion were characteristic of acute idiopathic polyneuropathy; a rapid onset of a mainly motor neuropathy with eventual recovery. Nerve conduction studies performed during the second and third episodes demonstrated grossly slowed motor conduction velocities. The sural nerve was biopsied after the third episode, and the features seen on light and electron microscopy included prominent hypertrophic changes, mononuclear cells associated with most "onion bulbs" and macrophage mediated demyelination. Studies of blastogenesis and macrophage migration inhibition, showed T lymphocyte responsiveness to both peripheral nerve myelin and tetanus toxoid. Typing for antigens of the HLA system indicated that the patient was homozygous for HLAB8.


A semi-automated robotic system for percutaneous interventions.
A robotic assistive device is developed for needle-based percutaneous interventions. The aim is a hybrid system using both manual and actuated robotic operation in order to obtain a device that has a large workspace but can still fit in the gantry opening of a CT scanner. This will enable physicians to perform precise and time-efficient CT-guided percutaneous interventions. The concept of the mechanics and software of the device is presented in this work. The approach is a semi-automated robotic assistive device, which combines manual and robotic positioning to reduce the number and size of necessary motors. The system consists of a manual rough positioning unit, a robotic fine positioning unit and an optical needle tracking unit. The resulting system has eight degrees of freedom, of which four are manual, which comprise encoders to monitor the position of each axis. The remaining four axes are actuated axes for fine positioning of the needle. Cameras are attached to the mechanical structure for 3D tracking of the needle pose. The software is based on open-source software, mainly ROS2 as robotic middleware, Moveit2 for trajectory calculation and 3D Slicer for needle path planning. The communication between the components was successfully tested with a clinical CT scanner. In a first experiment, four needle insertions were planned and the deviation of the actual needle path from the planned path was measured. The mean deviation from the needle path to the target point was 21.9 mm, which is mainly caused both by translational deviation (15.4 mm) and angular deviation (6.8°) of the needle holder. The optical tracking system was able to detect the needle position with a mean deviation of 3.9 mm. The first validation of the system was successful which proves that the proposed concept for both the hardware and software is feasible. In a next step, an automatic position correction based on the optical tracking system will be integrated, which is expected to significantly improve the system accuracy.


Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma.
Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m2 IV d 1, 2), etoposide (200 mg/m2 IV d 1-3), and dexamethasone (40 mg PO d 1-4) followed by filgrastim (10 mcg/kg/d sc. through collection). We successfully collected stem cells from all patients, with a median of 7.9×106/kg of body weight (range, 4.4 to 17.3×106/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.


Anesthetic efficacy of 4% Articaine with 1:100,000 epinephrine versus 4% articaine with 1:200,000 epinephrine as a primary buccal infiltration in the mandibular first molar.
No study has compared 4% articaine with 1:100,000 epinephrine with 4% articaine with 1:200,000 epinephrine in a mandibular buccal infiltration of the first molar. The authors conducted a prospective, randomized, double-blind, crossover study comparing the degree of pulpal anesthesia obtained with 4% articaine with 1:100,000 epinephrine and 4% articaine with 1:200,000 epinephrine as a primary infiltration in the mandibular first molar. Eighty-six asymptomatic adult subjects randomly received a primary mandibular buccal first molar infiltration of a cartridge of 4% articaine with 1:100,000 epinephrine and a cartridge of 4% articaine with 1:200,000 epinephrine in 2 separate appointments. The authors used an electric pulp tester to test the first molar for anesthesia in 3-minute cycles for 60 minutes after the injections. The two 4% articaine formulations showed no statistically significant difference when comparing anesthetic success, onset of anesthesia, or incidence of pulpal anesthesia. The anesthetic efficacy of 4% articaine with 1:200,000 epinephrine is comparable to 4% articaine with 1:100,000 epinephrine in a primary mandibular buccal infiltration of the first molar.


Main photophysical properties of oxyblepharismin.
Oxyblepharismin is the photo-oxidized form of blepharismin, the chromophore responsible for the photophobic response of heterotrich ciliate Blepharisma japonicum, and represents a nice model for the study of photo-transduction. In this work, we focused on the photophysical characterization of OxyBP, in view of highlighting the main features related to excitation and emission. By a combined experimental and computational approach we identified the main features of absorption and fluorescence emission of the molecule in solvents of different properties, identifying the nature of transitions as well as the possible heterogeneity at ground/excited state. The thorough photophysical characterization of OxyBP is meant to provide the starting point for the elucidation of the photo-transduction pathway in vivo.


The deficiency of a lysosomal acid hydrolase in two clones derived from the human lymphoblastoid line F137 after mutagen treatment.
Two clones (out of a total of 181 clones tested) derived from the human lymphoblastoid (lymphoid) line F137 after mutagen treatment were found to be deficient in a lysosomal acid hydrolase. The clone N32 derived from EMS-treated F137 is deficient in N-acetyl hexosaminidase A and B but contains normal levels of N-acetyl hexosaminidase C and low levels of an enzyme resembling N-acetyl hexosaminidase S. Thus the enzyme deficiency in this clone appears to resemble the so-called Sandhoff variant of Tay-Sachs disease, a disease inherited as an autosomal recessive condition. The clone G3 derived from MNNG treated F137 is deficient in alpha-galactosidase A. This clone resembles the situation in X-linked Fabry's disease. Karyotype analysis of the clones failed to reveal any chromosome rearrangement or losses of chromosomal material that might have accounted for the mutations and it is suggested that a single point mutation might in each case account for the loss of enzyme activity. No storage of the natural substrates of the two enzymes could be demonstrated in the clones.


Prognostic significance of controlling nutritional status in older adults with heart failure with preserved ejection fraction: a prospective comparative study with other objective nutritional indices.
We explored the prognostic significance of controlling nutritional status (CONUT) score in older adults with heart failure with preserved ejection fraction (HFpEF) and compared CONUT with other objective nutritional indices. This is a single-center retrospective cohort study in older adult coronary artery disease patients undergoing HFpEF. Clinical data and laboratory results were collected before discharge. CONUT, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI) were calculated according to the formula. The primary endpoint of this study was readmission due to heart failure and all-cause mortality in the first year after hospitalization. A total of 371 older adults were enrolled. All patients were discharged and followed up for 1 year, and readmission for heart failure was 26% while all-cause mortality was 20%. Compared with the none and mild malnutrition risk group, the readmission rate for heart failure (HF) within 1 year (36% vs. 18%, 23%) and all-cause mortality rate in the moderate and severe malnutrition risk group (40% vs. 8%, 0%) were higher (P < 0.05). On multivariate logistic analysis, CONUT was not associated with readmission due to HF within 1 year. CONUT was significantly associated with all-cause mortality independently of GNRI or PNI, after adjustment for major confounders including age, bedridden; length of stay; history of chronic kidney disease; loop diuretics use; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-adrenergic blocking agents use; New York Heart Association (NYHA) functional class; hemoglobin; potassium; Creatinine; triglycerides; glycosylated hemoglobin; brain natriuretic peptide; left ventricular ejection fraction; GNRI and PNI via multivariable Cox analysis (HR (95% CI) 1.764 (1.503, 2.071); 1.646 (1.359, 1.992); 1.764 (1.503, 2.071), respectively). Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with a higher CONUT (CONUT 5-12 compare to 0-1:HR (95% CI) 6.16 (3.78, 10.06); CONUT 2-4 compare to 0-1:HR (95% CI) 0.16 (0.10, 0.26)). CONUT showed the best area under the curve value (0.789) for the prediction of all-cause mortality compared with the other objective nutritional indices. CONUT is a simple and strong prognostic indicator for the prediction of all-cause mortality in older adults with HFpEF. NCT05586828.


Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs.
We examined the role of excitatory amino acids (EAAs) in activation of noradrenergic locus coeruleus (LC) neurons evoked by electrical stimulation of the medial prefrontal cortex (mPFC) in halothane-anesthetized rats. Microinfusion of the specific N-methyl-D-aspartate antagonist 2-amino-5-phosphonopentanoic acid (AP5, 50 or 100 microM) into the LC significantly suppressed LC responses evoked by mPFC stimulation. Microinfusion of the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 25 or 50 microM) also significantly reduced evoked LC responses. Simultaneous microinfusion of both AP5 and CNQX considerably increased the proportion of LC neurons which exhibited complete suppression of evoked responses (81%), compared to either AP5 or CNQX alone (approximately 50% each). These results indicate that LC activation by mPFC stimulation is mediated by both NMDA- and non-NMDA-type EAA channels.


Dynamic three-dimensional shoulder kinematics in patients with massive rotator cuff tears: a comparison of patients with and without subscapularis tears.
Massive rotator cuff tears (MRCTs) with subscapularis (SSC) tears cause severe shoulder dysfunction. In the present study, the influence of SSC tears on three-dimensional (3D) shoulder kinematics during scapular plane abduction in patients with MRCTs was examined. This study included 15 patients who were divided into two groups: supraspinatus (SSP) and infraspinatus (ISP) tears with SSC tear (torn SSC group: 10 shoulders) or without SSC tear (intact SSC group: 5 shoulders). Single-plane fluoroscopic images during scapular plane elevation and computed tomography (CT)-derived 3D bone models were matched to the fluoroscopic images using two-dimensional (2D)/3D registration techniques. Changes in 3D kinematic results were compared. The humeral head center at the beginning of arm elevation was significantly higher in the torn SSC group than in the intact SSC group (1.8±3.4 mm vs. -1.1±1.6 mm, p<0.05). In the torn SSC group, the center of the humeral head migrated superiorly, then significantly downward at 60° arm elevation (p<0.05). In the intact SSC group, significant difference was not observed in the superior-inferior translation of the humeral head between the elevation angles. In cases of MRCTs with a torn SSC, the center of the humeral head showed a superior translation at the initial phase of scapular plane abduction followed by inferior translation. These findings indicate the SSC muscle plays an important role in determining the dynamic stability of the glenohumeral joint in a superior-inferior direction in patients with MRCTs.


Severe Pulmonary Hypertension in a Patient with Scurvy: Can a Vitamin Reverse It?
Pulmonary hypertension secondary to scurvy is a rare manifestation that historically has not been well studied and is only described in a handful of case reports. Our case is about a 35-year-old female with a history significant for drug and tobacco abuse, obesity, poor diet, anxiety, and major depressive disorder who was found to have severe pulmonary hypertension in the setting of vitamin C deficiency (<0.01 mg/L). We present a case that shows pulmonary hypertension can be associated with scurvy and reversed rapidly with adequate vitamin C supplementation.


Predictive validity of the Undergraduate Medicine and Health Sciences Admission Test for medical students' academic performance.
To determine the predictive validity of the Undergraduate Medicine and Health Sciences Admission Test (UMAT) for academic performance at university. We studied all 339 students who entered medical study at the School of Medicine, University of Queensland, directly from high school, between 2005 and 2009. UMAT scores before entry compared with grade point averages (GPAs) during university study. Mean overall UMAT score at entry was 60/100 and mean GPA during university study was 6.1 (range, 1-7), with a correlation coefficient of 0.15 (P = 0.005). This relationship existed only in the first year of university study. For UMAT Section 1 score, the correlation coefficient was 0.14 (P = 0.01); for UMAT Section 2, the correlation coefficient was 0.06 (P = 0.29); and for UMAT Section 3, the correlation coefficient was 0.09 (P = 0.11). UMAT overall score for men (60.2) and women (59.8), and GPA for men (6.1) and women (6.2) were similar. However, men performed better in Section 1 (mean score 61.6 v 61; P = 0.05) and Section 3 (63.2 v 60.7; P < 0.001), whereas women performed better in Section 2 (58.5 v 55.8; P = 0.009). In multivariate analysis, only correlation between GPA and UMAT Section 1 score remained significant but was weak and lasted for 1 year of university study. Our findings suggest that UMAT has limited predictive validity for academic performance.


The use of autologous bone for augmentation procedures leads to low prevalence of peri-implantitis-a retrospective study over a 20-year period.
The aim of this study was to compare the prevalence of peri-implantitis in implants inserted into pristine bone (control) to implants where autologous bone was used for grafting procedures (study). All patients who underwent implant surgery during a 20 years interval by one maxillofacial implant surgeon and received a prosthodontic rehabilitation afterwards were eligible for inclusion in the study. Periimplant bone resorption and periimplant disease were assessed. Of 421 patients 384 (91.2%) patients responded to a recall after having been treated over a 20-year period by one maxillofacial surgeon and several dentists. A total of 110 patients had 239 implants in pristine bone, and 274 patients had 607 implants placed in combination with autologous bone grafting procedures. Mean time in function was 74 months (range 15-236 months). In all, 342 implants (34.8%) were in function for longer than 7 years. A total of 64 implant sites (7.6%) in 39 patients (10.2%) showed signs of peri-implant mucositis. In addition, 17 implants (2.0%) in 14 patients (3.6%) revealed signs of peri-implantitis, of which five implants were in the control group (2.09%) whereas 12 implants were in the study group (1.98%), with no statistically significant difference (p = 0.8405). More than half of the patients with peri-implantitis had a history of periodontitis. Three implants were lost due to peri-implantitis and four implants failed for other reasons, resulting in an overall success rate of 99.2% in 846 implants. CONCLUSIONS: Within the limitations of the study it seems that the use of autologous bone still is a relevant option when performing augmentation procedures because of the low prevalence of peri-implantitis.


Increased levels of IL-17A in serum and amniotic fluid of pregnant women with acute toxoplasmosis.
This study detected and compared the levels of Il-17A, IFN-gamma and IL-10 in the amniotic fluid (AF) and serum of pregnant women with acute toxoplasmosis in southern Brazil. It also compared the serum levels of these mediators in pregnant women with acute or chronic toxoplasmosis and with uninfected women. The serological investigations of anti-T. gondii IgM and IgG from the 60 pregnant women were determined by chemiluminescence microparticle immunoassay (CMIA). Twenty patients were uninfected, twenty were in the chronic phase and twenty were in the acute phase of toxoplasmosis. The 20 pregnant women in acute phase all agreed with amniocentesis. Serum and AF cytokines were evaluated by sandwich enzyme-linked immunosorbent assay. The analyzed cytokines showed no significant difference in blood versus amniotic fluid levels of pregnant women in the acute toxoplasmosis. Furthermore, we observed that serum IL-17A was significantly higher in pregnant women in the acute phase of infection compared to pregnant women with chronic toxoplasmosis and seronegative pregnant women. T. gondii DNA was not amplified in any of the samples of amniotic fluid by the nested-PCR reaction. Serum IL-10 levels were also higher in negative pregnant women than in infected pregnant women. Our findings indicate the activation of an inflammatory response to infection by T. gondii and suggest that increased production of IL-17A may be a protective factor against infection of the fetus.


Evaluating alternative electrostatic potential models for polyacrylamide-co-acrylate in aqueous solution.
The capabilities of three simplified analytical equations to accurately model electrostatic interactions during proton binding and release by linear anionic polyelectrolytes in aqueous solution were evaluated. The impermeable sphere (IS), Donnan (DN), and cylindrical (CY) electrostatic models were fit to experimental acid-base titration curves of linear polyacrylamide-co-acrylate having ionizable site densities ranging from ca. 10-35%. The titrations were conducted in 0.003-0.12M NaCl solutions and the sum of squared errors from modeled and experimental data was used as a comparative index of each model's capability. In addition, the relative size of each polyelectrolyte was estimated from its measured specific viscosity and then compared against the values obtained from the fitting procedure for the size parameter that each model contained. Although the IS and DN electrostatic models could be used to obtain reasonably good fits to each titration curve, the size parameter values obtained by each model were not reflective of the actual polyelectrolyte sizes, indicating that the models had limited physical meaning and that the size parameter was essentially just an additional fitting parameter in each model. In contrast, the CY model was not only more effective in its ability to fit the titration data but also provided a better physical representation of the polyelectrolyte size. Therefore, for polyelectrolytes that remain essentially linear or are only loosely coiled such that counter ions are free to travel throughout the polymer structure, we conclude that the CY model and its morphological representation of a cylindrical polyelectrolyte are more valid and realistic than the IS and DN models and their representation of polyelectrolytes as spheres.


Ultrathin NiV Layered Double Hydroxide for Methanol Electrooxidation: Understanding the Proton Detachment Kinetics and Methanol Dehydrogenation Oxidation.
Electrochemical methanol oxidation reaction (MOR) is regarded as a promising pathway to obtain value-added chemicals and drive cathodic H2 production, while the rational design of catalyst and in-depth understanding of the structure-activity relationship remains challenging. Herein, the ultrathin NiV-LDH (u-NiV-LDH) with abundant defects is successfully synthesized, and the defect-enriched structure is finely determined by X-ray adsorption fine structure etc. When applied for MOR, the as-prepared u-NiV-LDH presents a low potential of 1.41 V versus RHE at 100 mA cm-2 , which is much lower than that of bulk NiV-LDH (1.75 V vs RHE) at the same current density. The yield of H2 and formate is 98.2% and 88.1% as its initial over five cycles and the ultrathin structure of u-NiV-LDH can be well maintained. Various operando experiments and theoretical calculations prove that the few-layer stacking structure makes u-NiV-LDH free from the interlayer hydrogen diffusion process and the hydrogen can be directly detached from LDH laminate. Moreover, the abundant surface defects upshift the d-band center of u-NiV-LDH and endow a higher local methanol concentration, resulting in an accelerated dehydrogenation kinetics on u-NiV-LDH. The synergy of the proton detachment from the laminate and the methanol dehydrogenation oxidation contributes to the excellent MOR performance of u-NiV-LDH.


Surface roughness effect on fatigue strength of aluminum alloy using revised stress field intensity approach.
The fatigue strength of a component is known to highly depend on its surface quality, and it is thus necessary to develop a reliable and appropriate mathematical model for fatigue strength assessment that consider the effect of surface roughness. In this paper, different underlying physical mechanisms of the roughness effect at different regions of specimens were studied by fatigue testing of 7N01 aluminum alloy. For a quantitative analysis of the surface roughness effect, a revised stress field intensity approach for a fatigue strength assessment of microsized notches was proposed as a theoretical support. In the new model, a new form of weight function was built to adapt the characteristics of microsized notches. In addition, the effect of the field radius was fundamentally weakened on solution of the stress field intensity and the difficulty of fatigue failure region definition in the traditional method was overcome correspondingly in the proposed model, which made the calculated field strength accurate and objective. Finally, to demonstrate the validity of the revised approach quantitatively, specimens with conventionally sized notches were subjected to stress field intensity calculations. The results showed that the revised approach has satisfactory accuracy compared with the other two traditional approaches from the perspective of quantitative analysis.


Clonal spread of methicillin-resistant coagulase-negative staphylococci among horses, personnel and environmental sites at equine facilities.
A cross-sectional study was carried out to investigate species distribution and clonality of methicillin-resistant coagulase-negative staphylococci (MRCoNS) isolated from the nasal cavity of 39 horses and 32 veterinary or caretaker staff, and from 76 environmental surfaces at three equine facilities in Denmark. MRCoNS obtained by selective isolation were characterised by 16S rDNA sequencing, PCR detection of mecA, and pulsed-field gel electrophoresis (PFGE). MRCoNS were found in 32 (82%) horses, 20 (63%) humans and 50 (66%) environmental samples. The most common species was S. vitulinus (n=56), followed by S. sciuri (n=25), S. haemolyticus (n=14). Undistinguishable PFGE patterns were observed in MRCoNS of equine, human and environmental origin. A S. vitulinus clone and a S. haemolyticus clone were isolated from multiple horses, staff members and environmental sites within a farm and a veterinary hospital, respectively. The results indicated that methicillin-resistant strains of these two species can be shared by and possibly exchanged between horses and personnel, either directly or through contaminated environments.


Predominance of international clone 2 OXA-23-producing-Acinetobacter baumannii clinical isolates in Greece, 2015: results of a nationwide study.
In a previous nationwide study in Greece, OXA-58 was the sole carbapenemase present among carbapenem-resistant Acinetobacter baumannii (CRAB) isolated between 2000 and 2009. In this study, the antibiotic resistances, carbapenemase gene content and clonal relatedness of 194 single-patient CRAB clinical isolates collected randomly during 2015 from 11 tertiary hospitals located throughout Greece were investigated. Antimicrobial susceptibility was determined using commercial and dilution methods. PCR assays for carbapenemase genes were performed. Clonality was tested by a scheme based on two multiplex PCRs and single-locus blaOXA-51-like sequence-based typing. Furthermore, Pasteur's multilocus sequence typing (MLST) scheme and pulsed-field gel electrophoresis (PFGE) were applied to 31 selected representative isolates. The most active antibiotics were trimethoprim/sulfamethoxazole (SXT) (34.6% of isolates susceptible), minocycline (71.6%), colistin (72.7%) and tigecycline (MIC50/90 values, 1/2 mg/L). The blaOXA-23-like gene was identified in 188 isolates (96.9%), blaOXA-23-like together with blaOXA-58-like in 3 isolates (1.5%), blaOXA-58-like in 2 isolates (1.0%) and blaOXA-40-like in 1 isolate (0.5%). ISAba1 was found upstream of the blaOXA-23-like gene in all isolates. International clone (IC) 2 comprised 157 isolates (80.9%), IC1 comprised 36 isolates (18.6%) and ST78 comprised 1 isolate (0.5%). All IC2 and IC1 isolates tested by MLST were ST2 and ST1, respectively. Seven PFGE types were detected. IC2 isolates were resistant to more antibiotics than IC1, except for SXT. This nationwide study showed that CRAB isolates in Greek hospitals currently produce almost uniformly the OXA-23 carbapenemase and belong mainly to IC2 and, to a lesser extent, IC1. Of particular concern, colistin susceptibility is recently severely reduced.


Multi-frequency shear modulus measurements discriminate tumorous from healthy tissues.
As far as their mechanical properties are concerned, cancerous lesions can be confused with healthy surrounding tissues in elastography protocols if only the magnitude of moduli is considered. We show that the frequency dependence of the tissue's mechanical properties allows for discriminating the tumor from other tissues, obtaining a good contrast even when healthy and tumor tissues have shear moduli of comparable magnitude. We measured the shear modulus G*(ω) of xenograft subcutaneous tumors developed in mice using breast human cancer cells, compared with that of fat, skin and muscle harvested from the same mice. As the absolute shear modulus |G*(ω)| of tumors increases by 42% (from 5.2 to 7.4 kPa) between 0.25 and 63 Hz, it varies over the same frequency range by 77% (from 0.53 to 0.94 kPa) for the fat, by 103% (from 3.4 to 6.9 kPa) for the skin and by 120% (from 4.4 to 9.7 kPa) for the muscle. These measurements fit well to the fractional model G*(ω)=K(iω)n, yielding a coefficient K and a power-law exponent n for each sample. Tumor, skin and muscle have comparable K parameter values, that of fat being significantly lower; the p-values given by a Mann-Whitney test are above 0.14 when comparing tumor, skin and muscle between themselves, but below 0.001 when comparing fat with tumor, skin or muscle. With regards the n parameter, tumor and fat are comparable, with p-values above 0.43, whereas tumor differs from both skin and muscle, with p-values below 0.001. Tumor tissues thus significantly differs from fat, skin and muscle on account of either the K or the n parameter, i.e. of either the magnitude or the frequency-dependence of the shear modulus.


Hematoporphyrin and hematoporphyrin-derivative photosensitization of mitochondria.
Laser micro-irradiation experiments show that mitochondria are profoundly affected when cells are irradiated with Hp as the photosensitizer. Functional as well as enzymatic studies on isolated mitochondria show that coupling between respiration and oxidative phosphorylation, Ca2+ transport and respiration are successively lost under irradiation in the presence of either Hp or HpD. ATP-driven Ca2+ uptake, which is not impaired under anoxic conditions with HpD alone, is impaired in the absence of oxygen by the synergistic action of HpD and nitroimidazoles.


Allergy to white potato.
Allergy to potato is uncommon, and even more uncommon is allergy to potato pollen. The occurrence of both phenomena in the same patient made it possible to study cross-reactivity patterns of potato antigens. An 11-year-old girl, exclusively breast-fed for her first 4 months, developed anaphylactic symptoms after ingestion of potato at 5 months of age when she was fed potato for the first time. Subsequently, she developed urticaria, angioedema, and respiratory and systemic symptoms on contact with potatoes, ingestion of potatoes, and exposure to cooking potatoes or potato pollen. Three allergenic extracts from potato pulp, peel, and pollen were prepared. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and isoelectrofocusing of the three extracts were performed. IgE-mediated allergy to these extracts was demonstrated by means of immediate skin test reactivity, positive passive transfer, RAST, RAST inhibition, and leukocyte histamine release. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the pulp extract followed by electroblotting and autoradiography demonstrated specific IgE antibodies directed against several proteins ranging from 14,000 to 40,000 daltons.


Expert Perspectives on the Performance of Explosive Detection Canines: Operational Requirements.
Explosive detection canines (EDC) play an important role in protecting people and property. The utilization of and research on EDCs is often based on personal experience or incomplete knowledge. EDC practitioners (handlers, trainers, and leaders) possess the institutional knowledge necessary to understand EDC operational requirements. This study utilized a qualitative approach with semi-structured interviews of EDC experts (n = 17) from across the employment spectrum. The interviews elicited EDC expert perceptions of the performance of the EDC team and the operational requirements in the physical, climate, operational, and explosive odor environments. Analysis of the data revealed commonalities across all EDCs and utilization-specific differences. To be effective, the EDC team must function well on both ends of the leash, and the handler likely has the greatest impact on the EDC's performance. Common requirements include expectations to perform at a high level in a variety of manmade and natural physical environments and under a range of climate conditions. EDCs must work through the visual, olfactory, and auditory challenges of the operational environment and the countermeasure efforts of those utilizing explosive devices. Utilization-specific differences like patrol or assault training and utilization add additional requirements for some EDCs. The results of this study can be used to inform EDC selection, training, assessment, and deployment, and further research into EDC performance.


Cardiovascular dynamics during classical appetitive and aversive conditioning in laboratory primates.
This report describes changes in the rate of rise of left and right intraventricular pressures during aversive and appetitive conditioning procedures in chair-restrained rhesus monkeys. The conditioning paradigm consisted of a one-minute tone followed, in the one case, by an electric shock, and in the other, by the delivery of Purina monkey pellets. The conditional cardiovascular response was characterized by short latency, highly significant elevations in the derivatives of both ventricular pressures as well as a marked arterial pressor response and tachycardia. The magnitude of the conditional response to the classical aversive procedure was somewhat larger than that to appetitive conditioning. These alterations in the rate of development of intraventricular pressure can be attributed largely to augmentation in the sympathetic neural input to the heart and contribute to an analysis of selective aspects of the nervous regulation of the heart in intact, behaviorally conditioned animals.


Midterm Outcomes for Isolated Coronary Artery Bypass Grafting in Octogenarians.
An increase in the life expectancy of the general population has led to heightened numbers of elderly patients in need of coronary artery bypass grafting (CABG). Surgical revascularization in octogenarians is becoming more commonplace, and outcomes in this cohort continue to gain relevance. All patients who underwent isolated CABG (n = 7048) at the University of Pittsburgh Medical Center from 2010 to 2017 were reviewed. A comparative analysis between octogenarians (≥80 years) and septuagenarians (70-79 years) was performed with primary outcomes that included all-cause mortality and readmission at 30 days, 1 year, and 5 years. The total patient population consisted of 2226 patients who were divided into two age groups, including 1673 septuagenarians (75.2%) and 553 octogenarians (24.8%). Mean age was 74.19 ± 2.80 years versus 82.94 ± 2.57 years (P < .001) for the first and second cohort, respectively. The octogenarian group had higher operative risk represented by a mean Society of Thoracic Surgeons Predicted Risk of Mortality of 6.03% ± 6.42% (P < .001). Operative mortality was higher in octogenarians (5.24% versus 2.69%; P = .004). Predictors of long-term mortality included chronic lung disease (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.43-2.17; P < .001), emergent status (HR = 2.09; 95% CI, 1.34-3.28; P = .001), and peripheral artery disease (HR = 1.61; 95% CI, 1.31-1.97; P < .001). Patients 80 years and older had increased risk of both cardiac readmission (HR = 1.2; 95% CI, 1.03-1.40; P = .02) and heart failure readmission (HR = 1.53; 95% CI, 1.23-1.91; P < .001). CABG can be performed in octogenarians with acceptable survival although they have an increased risk of readmission for cardiac causes, specifically, higher rates of heart failure.


Outcomes of lymphadenectomy for lymph node recurrence after esophagectomy or definitive chemoradiotherapy for squamous cell carcinoma of the esophagus.
The aim of this study was to determine the significance of lymphadenectomy for recurrence after treatment for esophageal squamous cell carcinoma. Short- and long-term outcomes of 24 patients who underwent lymphadenectomy for recurrence in 3 hospitals between April 2004 and March 2013 were retrospectively analyzed. There were 17 cases with lymph node recurrence after esophagectomy (11 cervical, 4 mediastinal, and 2 abdominal node recurrences) and 7 cases with remnant or recurrent lymphatic diseases after definitive chemoradiotherapy (3 cervical, 1 mediastinal, and 3 abdominal node recurrences). Three minor complications were observed among 24 patients and the median postoperative hospital stay was 7 days. The 3-year progression-free and overall survivals of patients who underwent secondary lymphadenectomy for recurrence after esophagectomy were 51.5 and 75.5 %, respectively. The overall survival of patients with cervical node recurrence was significantly better than that of patients with mediastinal or abdominal node recurrence in this group (P = 0.0097). The median progression-free and overall survivals of patients who underwent salvage lymphadenectomy after definitive chemoradiotherapy were 2 and 15 months, respectively. Although only 1 patient experienced local recurrence after secondary lymphadenectomy, locoregional failures occurred in 6 of 7 patients who underwent salvage lymphadenectomy after definitive chemoradiotherapy. Secondary or salvage lymphadenectomy can be performed safely in the selected patients. Secondary lymphadenectomy achieves locoregional disease control and results in a favorable long-term outcome, particularly for cervical node recurrence. Further large-scale cohort studies are needed to determine the prognostic significance of salvage lymphadenectomy after definitive chemoradiotherapy.


Effects of tetrodotoxin on the slowly adapting stretch receptor neurone of lobster.
1. A study has been made of the effects of tetrodotoxin on the impulse activity, resting membrane potential, input resistance, and the generator potential and its after-hyperpolarization of the slowly adapting stretch receptor neurone of the lobster.2. Tetrodotoxin was able to abolish completely within about 2 min the impulse activity in most cells, when given in a dose of 2 x 10(-8) g/ml., but in all cells, when administered in a dose of 4 x 10(-8) g/ml. After blockage by the toxin in concentrations as high as 4 x 10(-6) g/ml. for periods of up to 30 min the action potential was restored by washing the preparation in physiological solution for 1 hr.3. In a concentration of 4 x 10(-8) g/ml. tetrodotoxin produced within 1-2 min an average increase of 4.8 mV of the resting membrane potential and a simultaneous 47% reduction of the resting input resistance. These effects were reversed by washing the preparation in physiological solution for 1 hr.4. Tetrodotoxin administered in doses as high as 4 x 10(-6) g/ml. for periods of up to 30 min had no effect on the amplitude of the steady phase of the generator potential.5. In a concentration of 4 x 10(-8) g/ml. tetrodotoxin produced within 5 min a 65% reduction of the amplitude of the hyperpolarization following the generator potential. This effect was reversed by washing the preparation in physiological solution for 1 hr.6. The simultaneous increase in resting membrane potential and decrease in membrane resistance is suggested to be due to an elevated potassium permeability besides a reduced sodium conductance. The constancy in height of the generator potential in the presence of a decreased membrane resistance makes necessary the assumption of an augmented generator current. The decrease in amplitude of the hyperpolarization following the generator potential may be the result of an increase in potassium conductance and/or a reduction in acceleration of an electrogenic pump in consequence of a diminished sodium influx during the generator potential.


The availability to the rat of energy from various diet ingredients.
The digestible and metabolizable energy values of 8 ingredients commonly used in laboratory animal diets were determined using the growing male rat, by the total collection method. Each ingredient was incorporated into a basal diet of maize, wheat, soyabean meal and fishmeal. The metabolizable energy values, on a dry matter basis, corrected to the nitrogen retention of the basal diet for rats per 100 g bodyweight were as follows: maize 15.23 MJ/kg, extracted soyabean meal 14.11 MJ/kg, barley 12.31 MJ/kg, wheat 14.09 MJ/kg, oatfeed 1.36 MJ/kg, white fishmeal 11.61 MJ/kg, dried skimmed milk 14.32 MJ/kg, casein 17.91 MJ/kg. Additional analytical data for the 8 ingredients are also given.


Impact of choice of volumetry software and nodule management guidelines on recall rates in lung cancer screening.
Appropriate lung nodule management is essential to minimizing unnecessary patient recall in lung cancer screening. Two European guidelines provide differing recommendations in that participants with nodules ≥100 mm3 or ≥80 mm3 respectively should be recalled, at baseline. Nodule size estimation is known to vary between volumetry software packages (VSPs). The aim of this study was to examine the impact of choice of VSP on participant recall rates, when applying different European nodule management guidelines. An additional aim was to compare recall rates between 7 VSPs and manual diameter measurements. 156 small-sized lung nodules (50-150 mm3) from the UK Lung Screening trial were measured using 7 different VSPs (VSP1-7) and also using manual diameter. The type of VSP used in the NELSON study (VSP1), on which European nodule management guidelines are based, provided the reference standard. Nodule size was compared using Bland Altman, and recall rates by Mcnemar's test. Compared to the reference standard, a 100 mm3 threshold for recall, resulted in no difference in recall rates only for VSP 5 & 7. Using an 80mm3 threshold resulted in no difference in recall rates for VSP2 & 6. Recall rates were significantly higher for VSP 4 regardless of threshold and when using manual diameter measurements. Appropriate nodule size thresholds for recall in screening depend on the type of volumetry software used. The results highlight the importance of benchmarking of volumetry packages.


The clinical significance of immediate symptom responses to manual therapy treatment for neck pain: observational secondary data analysis of a randomized trial.
The objective was to explore aspects of symptom responses to manual therapy treatment for neck pain. An observational secondary data analysis of a randomized trial was conducted. 181 participants seeking care from a physiotherapist or chiropractor for a new episode of neck pain were included. Outcome variables included recovery-time and participant-perceived effect of treatment (GPE) at 3-months. There was a significant reduction of ≥1.4 points (95%CI 1.2-1.5) in pre- and post-treatment pain scores at each occasion of treatment. There was also small but significant increases in pain of ≤0.7 points (95%CI 0.4-1.0) between each treatment session, without regression to the preceding pre-treatment level. The relationships between immediate post-treatment effects and longer-term outcomes were explored using multivariate regression analyses. There was significant univariate association between recovery time and cumulative post-treatment changes in pain from the second, third and fourth (Exp(B) = 1.2) treatment sessions, as well as the presence of post-treatment headache (Exp(B) = 0.7) and other minor adverse symptoms (Exp(B) = 0.6). There was significant univariate association between GPE at 3-months and cumulative pain responses from first (B = 0.2), second (B = 0.3), third (B = 0.3) and fourth (B = 0.4) treatment sessions. The change in pain after session 1 was independently associated with GPE (B = 0.2). There was a consistently significant difference of ≥0.7 points (95%CI 0.43-0.89) in the different methods of reporting pain. Our results showed that manual therapy for neck pain involves a "two-steps forward, one-step back" recovery pattern. Whilst minor adverse events are undesirable, they do not seem to be significantly associated with long-term recovery.


Cost/benefit analysis of pharmacologic hemostasis.
Surgical bleeding with possible associated coagulopathies is a major source of morbidity and mortality. More than 27% of patients receive unnecessary blood or blood-product transfusions during cardiac operations. Analysis of the cost-benefit of pharmacologic hemostasis can be accomplished by relating all the components of cost, which include both direct and indirect costs to both direct and indirect benefits to the patient. A significant reduction in transfusion requirements can be achieved by the systematic application of a clinical algorithm. An alternative is to use drugs that enhance hemostasis. Four such drugs commonly used are desmopressin acetate, tranexamic acid, epsilon-aminocaproic acid, and aprotinin. All these agents have been shown to successfully reduce bleeding and the need for transfusion. It appears that the order of efficacy (greatest to least) is aprotinin, tranexamic acid, epsilon-aminocaproic acid, and desmopressin acetate. Cost/benefit analysis associated with the use of these agents is complex. The direct costs of these drug treatments can be balanced against the costs related to blood and blood-product administration. Using epsilon-aminocaproic acid, blood used is valued at $30, whereas the drug treatment cost is less than $2. Aprotinin use results in costs of more than $500, with the drug costing $900. Improved hemostasis should also result in indirect cost savings from reduced operating room time, reduced intensive care unit and hospital stay, and the avoidance of reoperation for bleeding.