Establishing minimally invasive cardiac surgery in a low-volume mitral surgery centre.

INTRODUCTION: Despite early enthusiasm, minimally invasive cardiac surgery has had a low uptake compared with novel techniques in interventional cardiology. Steep learning curves from high-volume centres have deterred smaller units from engaging, even though low-volume centres undertake a large proportion of surgical interventions worldwide. We sought to identify the safety and experience of learning minimally invasive cardiac surgery after undertaking a structured fellowship at Blackpool Victoria Hospital, a low-volume centre. MATERIALS AND METHODS: A retrospective analysis of outcomes for all consecutive minimally invasive cardiac surgery procedures performed via a right mini-thoracotomy at our institution between 2007 and 2017 was undertaken. Clinical outcomes included death, conversion to sternotomy, stroke, renal failure and other organ support. Cardiopulmonary bypass, aortic cross-clamp times and learning cumulative sum sequential probability method curves were also assessed to determine how safely the procedure was adopted. RESULTS: A total of 316 patients were operated on for mitral, tricuspid, atrial fibrillation, septal defects or other conditions. The mean logistic European System for Cardiac Operative Risk Evaluation score was 7.0 (± 8.5). Conversion to sternotomy occurred in 12 patients (3.8%) and in-hospital mortality was 7 (2.2%). None of the converted patients died. The learning curves showed an accelerated process of adoption, similar to reference figures from a high-volume German centre. DISCUSSION: It is possible for low-volume cardiac surgical centres to undertake minimally invasive surgical programmes with good outcomes and short learning curves. Despite technical complexities, with a team approach, the learning curve can be navigated safely.

Data on the annealing of NbTiVZr at 1200 °C with slow cooling rate.

The data presented here is complementary to the publication entitled "High temperature, low neutron cross-section high-entropy alloys in the Nb-Ti-V-Zr system" [1]. A homogenization methodology with slower cooling rate (∼2 °C/min) was performed. X-ray diffraction and scanning electron microscopy (backscattered electron and energy dispersive spectroscopy) data pertaining to annealed high-entropy alloy composition NbTiVZr is presented.

Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection.

BACKGROUND: The novel Malawi polyomavirus (MWPyV) was initially detected in stool specimens from healthy children and children with gastrointestinal symptoms, mostly diarrhea, indicating that MWPyV might play a role in human gastroenteric diseases. Recently, MWPyV sequences were additionally identified in respiratory secretions from both healthy and acutely ill children suggesting that MWPyV may have a tropism for different human tissues. This study was designed to investigate the possible sites of latency/persistence for MWPyV in a cohort of healthy Italian children. METHODS: Specimens (n° 500) of tonsils, adenoids, blood, urines and feces, from 200 healthy and immunocompetent children (age range: 1-15 years) were tested for the amplification of the MWPyV LT antigen sequence by quantitative real-time PCR. Samples (n° 80) of blood and urines from 40 age-matched children with autoimmune diseases, were screened for comparison. Polyomaviruses JC/BK and Epstein-Barr Virus (EBV) were also tested as markers of infection in all samples using the same molecular technique. RESULTS: In our series of healthy children, MWPyV was detected only in the lymphoid tissues showing a prevalence of 6 % in tonsils and 1 % in adenoids, although with a low viral load. No JCPyV or BKPyV co-infection was found in MWPyV positive samples, while EBV showed a similar percentage of both in tonsils and adenoids (38 and 37 %). Conversely, no MWPyV DNA was detected in stool from babies with gastroenteric syndrome. With regards to autoimmune children, neither MWPyV nor BKPyV were detected in blood, while JCPyV viremia was observed in 15 % (6/40) of children treated with Infliximab. Urinary BKPyV shedding was observed in 12.5 % (5/40) while JCPyV in 100 % of the samples. CONCLUSIONS: The detection of MWPyV sequences in tonsils and adenoids of healthy children suggests that secondary lymphoid tissues can harbour MWPyV probably as transient sites of persistence rather than actual sites of latency.

Report on a clinical evaluation of the KerraPro Heel silicone heel pad.

Heels are at increased risk of injury due to the posterior prominence and lack of padding over the calcaneus. Pressure injuries, once established, are extremely costly, both in terms of the detrimental effect on psychosocial wellbeing and threat to life, as well as financially due to length of hospital stay and resources used to heal the wounds. A new and inexpensive silicone heel pad has been designed to simplify the necessary decisions and to address the problems associated with pressure injuries to the heels. This article will describe an observational evaluation of the product. KerraPro Heel pads were evaluated in two separate cohorts of 17 participants over a 4-week period with the primary aim to evaluate the efficacy of the product in preventing and alleviating pressure injuries on the heels. All participants had been reported as 'at risk' or 'at high risk' of pressure injury to the heels and had a history of developing such lesions. The KerraPro heel pads were compared with the participant's standard protocol. The outcome of the evaluation demonstrated the effectiveness of the KerraPro Heel pads in the prevention and treatment of heel pressure injuries.

Primary cervical lymphoma: a rare presentation to a genitourinary medicine clinic.

Primary non-Hodgkin's lymphoma of uterine cervix is a rare diagnosis. We present the case of a 47-year-old woman who presented to our genitourinary (GU) medicine service complaining of a malodorous discharge. Speculum examination revealed a necrotic mass on the cervix. She was referred urgently to gynaecology and subsequent histology revealed a diffuse large B-cell lymphoma. She received six cycles of RCHOP chemotherapy and is now in clinical remission. This case highlights the need for GU medicine physicians to remain vigilant with regard to possible gynaecological malignancies in all of our patients, the need for medical backup within GU medicine clinics and for clear pathways of referral to other specialists to exist.

Resilience among Japanese atomic bomb survivors.

AIM: The purpose of the study was to explore the experience of atomic bomb survivors from Hiroshima and Nagasaki. BACKGROUND: Never has the world experienced such extreme devastation as with the atomic bombings of Hiroshima and Nagasaki, Japan, in August 1945. Although significant quantitative research has been completed about the medical effects following radiation, the literature lacks qualitative exploration from a holistic health perspective. METHODS: This was a qualitative descriptive study, using methods of narrative analysis, oral history and ethnography. The sample for this research included eight individuals who were exposed to the atomic bombings in Japan and currently reside in the United States. FINDINGS: Findings provide insight to the resilience that the survivors exhibited immediately following the bomb, as well as throughout the 65 years following the event. From ethnographic data and interviews with survivors, a thematic structure was developed that depicts the essential elements of the atomic bomb experience. Two ways of being in the world followed the bombing: surviving and thriving, with resilience serving as a lever, allowing for fluid movement over time across the continuum. Individuals experiencing surviving exhibited anxiety about their personal and family members' health, expressed mistrust, and felt a stigma associated with being a survivor. For those who were thriving, peace activism, overcoming and forgiveness were typically displayed. CONCLUSION: Findings from this study add to the disaster nursing literature and highlight the role resilience plays in the atomic bomb survivors' life perspective.

Rotation of treatments between spinosad and amitraz for the control of Rhipicephalus (Boophilus) microplus populations with amitraz resistance.

A farmlet study was conducted over 4 years in which three treatments were applied to six groups of Holstein dairy calves. Calves in each group were infested with equal numbers of N-strain (susceptible) and Ultimo strain (amitraz and synthetic pyrethroid resistant) tick larvae to establish self-sustaining populations with an initial, measurable level of resistance to amitraz. Standard counts of all ticks between 4.5 and 8.0mm diameter on one side of each animal were made each week and treatment was applied when tick numbers exceeded a threshold of 25 engorged adults per side. The three treatments were: 1, spinosad spray whenever tick numbers exceeded the threshold; 2, amitraz spray whenever tick numbers exceeded the threshold; 3, spinosad whenever tick numbers exceeded the threshold for the first 2 months, then amitraz for 2 months, with alternation every subsequent 2 months. Engorged adult female ticks were collected from each treatment group on 10 or 11 occasions during the study and tested using the larval packet test bioassay (LPT) for acaricide resistance. Spinosad 250ppm provided effective control of amitraz-resistant tick populations in the field, using a similar number of treatments as in the amitraz and rotation groups. The initial infestations of all of the groups resulted in the establishment of populations with in vitro evidence of resistance to amitraz using the LPT. Treatment with spinosad or with a rotation between spinosad and amitraz every 2 months resulted in reduced levels of resistance to amitraz according to the LPT. The animals treated with amitraz alone showed increasing resistance to amitraz according to the LPT each summer and autumn with a return to full or almost full susceptibility to amitraz in early spring in all years. This pattern suggests a relative lack of fitness of amitraz-resistant ticks that might be exploited by using an acaricide rotation strategy.

Effects of age and gender on three-dimensional endoanal ultrasonography measurements: development of normal ranges.

BACKGROUND: Faecal incontinence is a common and morbid disorder that is often related to anal sphincter dysfunction. High-frequency, three-dimensional (3-D) endoanal ultrasonography (EAUS) allows greater spatial resolution and longitudinal appreciation of the anal canal than conventional 2-D assessment. A robust normal range of values allowing for age and sex is required for subsequent disease comparison. METHODS: A group of 30 healthy male (n=12) and female (n=18) volunteers (median age, 49 years; range, 31-63 years) underwent 3-D EAUS using a high-frequency 10-MHz transducer. A reconstructed data cube was interrogated to measure anal canal structures in 2-D at high, middle and low levels, and in 3-D for longitudinal measurements. RESULTS: Men had a significantly longer 3-D external anal sphincter (EAS) and internal anal sphincter (IAS) than women, especially the anterior EAS (mean in men 2.5 cm, mean in women 1.6 cm, p<0.0001). There were no significant differences between the sexes for anal canal length or by 2-D scanning for the thickness of the EAS and IAS. No significant differences were observed between parous and nulliparous women. Age had no significant effect on 3-D length measurements, but 2-D EAUS measurements of the thickness of both the IAS and EAS increased with age significantly (mid canal, p=0.004). On these bases, normal ranges were generated. CONCLUSIONS: Sphincter measurements, enabled by 3-D reconstruction, vary with age and sex. A normal range incorporating these variations has been produced for future data comparison in disease states.

Effectiveness and safety of olanzapine in the treatment of Asian outpatients with schizophrenia.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of olanzapine in the treatment of schizophrenia among Asian patients in an outpatient setting. METHODS: This was an open-label, prospective, observational study involving 339 patients from Indonesia, Pakistan, Malaysia, Thailand, and Singapore. Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Severity scale (CGI-S), and safety parameters were assessed. RESULTS: 62% of patients responded to olanzapine treatment, defined a priori as a reduction in BPRS of > 40% from baseline. Following the 8-week treatment period, the BPRS total, BPRS positive, BPRS negative, and CGI-S scores decreased by 18.7 (95% CI: 17.4, 20.2), 6.1 (5.6, 6.6), 2.9 (2.6, 3.2), and 1.5 points (median 1.0), respectively (p < 0.0001). In total, 31 of the 339 patients (9.1%) failed to complete the study according to the study description. Loss to follow-up and personal conflict were the most common reasons for discontinuation. There were 30 treatment-emergent adverse events with six serious cases, assessed as unrelated to study drug, reported. CONCLUSION: This study further demonstrates the effectiveness and safety of olanzapine in actual clinical practice settings, in reducing the severity of psychopathological symptoms in Asian patients with schizophrenia.

What is there left to learn about the Drosophila clock?

Circadian rhythms offer probably the best understanding of how genes control behavior, and much of this understanding has come from studies in Drosophila. More recently, genetic manipulation of clock neurons in Drosophila has helped identify how daily patterns of activity are programmed by different clock neuron groups. Here, we review some of the more recent findings on the fly molecular clock and ask what more the fly model can offer to circadian biologists.

Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8.

Nucleoside triphosphate diphosphohydrolases 1, 2, 3 and 8 (NTPDases 1, 2, 3 and 8) are the dominant ectonucleotidases and thereby expected to play important roles in nucleotide signaling. Distinct biochemical characteristics of individual NTPDases should allow them to regulate P2 receptor activation differentially. Therefore, the biochemical and kinetic properties of these enzymes were compared. NTPDases 1, 2, 3 and 8 efficiently hydrolyzed ATP and UTP with K (m) values in the micromolar range, indicating that they should terminate the effects exerted by these nucleotide agonists at P2X(1-7) and P2Y(2,4,11) receptors. Since NTPDase1 does not allow accumulation of ADP, it should terminate the activation of P2Y(1,12,13) receptors far more efficiently than the other NTPDases. In contrast, NTPDases 2, 3 and 8 are expected to promote the activation of ADP specific receptors, because in the presence of ATP they produce a sustained (NTPDase2) or transient (NTPDases 3 and 8) accumulation of ADP. Interestingly, all plasma membrane NTPDases dephosphorylate UTP with a significant accumulation of UDP, favoring P2Y(6) receptor activation. NTPDases differ in divalent cation and pH dependence, although all are active in the pH range of 7.0-8.5. Various NTPDases may also distinctly affect formation of extracellular adenosine and therefore adenosine receptor-mediated responses, since they generate different amounts of the substrate (AMP) and inhibitor (ADP) of ecto-5'-nucleotidase, the rate limiting enzyme in the production of adenosine. Taken together, these data indicate that plasma membrane NTPDases hydrolyze nucleotides in a distinctive manner and may therefore differentially regulate P2 and adenosine receptor signaling.

Overcoming the problem of non-ideal liquid ion exchanger selectivity in microelectrode ion flux measurements.

Ion-selective microelectrodes are a powerful tool in studies on various aspects of cell membrane biology in both animal and plant tissues. Further application of this technique is, however, limited to a large extent by the problem of non-ideal selectivity of the liquid ion exchanger used in the preparation of microelectrodes for ion flux measurements. Because of this problem, which is persistent in many commercial liquid ion exchangers, the microelectrode does not discriminate between the ion of interest and other interfering ions (for example, Mg2+ and Ca2+; Na+ and K+), thereby leading to inaccurate concentration readings and, consequently, inaccurate flux calculations. In this work we show that the existing analytical procedure to overcome this problem, using the inverted Nicolsky-Eisenman equation, is inadequate, and suggest an alternative analytical procedure that can be applied directly to the data obtained with commercially available liquid ion exchangers. We show that this alternative procedure allows accurate measurement of ionic concentrations with non-ideal ion-selective microelectrodes in the presence of interfering ions, and illustrate the method by direct experiment using Ca2+ and Mg2+ as a "case study". Several more examples are given, further illustrating practical applications of the method for study of plant responses to salinity, osmotic and reactive oxygen species stresses.

Higher skeletal muscle protein synthesis and lower breakdown after chemotherapy in cachectic mice.

The influence of cancer cachexia and chemotherapy and subsequent recovery of skeletal muscle protein mass and turnover was investigated in mice. Cancer cachexia was induced using colon 26 adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C(6)H(12)CIN(3)O(4)S). Reduced food intake was not a factor in these studies. Three days after cachexia began, healthy and tumor-bearing mice were given a single intraperitoneal injection of cystemustine (20 mg/kg). Skeletal muscle mass in tumor-bearing mice was 41% lower (P < 0.05) than in healthy mice 2 wk after cachexia began. Skeletal muscle wasting was mediated initially by decreased protein synthesis (-38%; P < 0.05) and increased degradation (+131%; P < 0.05); later wasting resulted solely from decreased synthesis (~-54 to -69%; P < 0.05). Acute cytotoxicity of chemotherapy did not appear to have an important effect on skeletal muscle protein metabolism in either healthy or tumor-bearing mice. Recovery began 2 days after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (-80%; P < 0.05) and later by increased protein synthesis (+46 to +73%; P < 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to protein synthesis and degradation.

Effects of trematode parasitism on the behaviour and ecology of a common marine snail (Littorina littorea (L.)).

Cryptocotyle lingua (Creplin) is a digenean trematode parasite of the littoral prosobranch gastropod Littorina littorea (L.). The literature suggests the snails become infected by grazing guano of the final host, the herring gull, Larus argentatus Pontoppidan. The parasite emerges from the snail as free-swimming cercariae. Interactions between the snail and the parasite at cellular and life-history levels are well established, but little is known of the influences the interaction has on the behaviour and the ecology of the snail. We tested the response of the snail to encounters with cercariae, examined the longevity of the guano on-shore and tested the responses of the snail to encounters with guano. Over half the L. littorea tested were able to detect both cercariae and a filtered homogenate of cercariae in conspecific mucus trails, approximately one-third of animals refusing to cross the treatments. Chemoreception by the mouth or foot is considered the most likely means of detection. Guano samples (mean weight 3.22 g) naturally deposited at approximately mid-tide level were completely washed away by one tidal inundation. We consider this period too brief to allow for ingestion of eggs in guano by the snail. Further, snails would not cross guano placed in conspecific trails. Most snails would not cross guano diluted by 10(3)x(10 mg ml(-1)) and some snails could still detect guano diluted by 10(6)x(10 &mgr;g ml(-1)), though all were prepared to cross it. Detection of guano is again believed to be by chemoreception by the mouth or foot. These results are discussed in terms of the mating and aggregating behaviour of L. littorea. Ingestion of the parasite by L. littorea is likely to take place once the guano has washed away as the eggs are negatively buoyant in seawater and may adhere to rock (biofilm) or algal fronds which may be grazed by the snail.

Regulation of chicken gizzard ecto-ATPase activity by modulators that affect its oligomerization status.

The major ectonucleoside triphosphate phosphohydrolase in the chicken gizzard smooth muscle membranes is an ecto-ATPase, an integral membrane glycoprotein belonging to the E-ATPase (or E-NTPDase) family. The gizzard ecto-ATPase is distinguished by its unusual kinetic properties, temperature dependence, and response to a variety of modulators. Compounds that promote oligomerization of the enzyme protein, i.e., concanavalin A, chemical cross-linking agent, and eosin iodoacetamide, increase its activity. Compounds that inhibit some ion-motive ATPases, e.g., sulfhydryl reagents, xanthene derivatives, NBD-halides, and suramin, also inhibit the gizzard ecto-ATPase, but not another E-ATPase, the chicken liver ecto-ATP-diphosphohydrolase, which contains the same conserved regions as the ecto-ATPase. Furthermore, inhibition of the gizzard ecto-ATPase by these compounds as well as detergents is not prevented by preincubation of the membranes with the substrate, ATP, indicating that their interaction with the enzyme occurs at a locus other than the catalytic site. On the other hand, the inhibitory effect of these compounds, except suramin, is abolished or reduced if the membranes are preincubated with concanavalin A. It is concluded that these structurally unrelated modulators exert their effect by interfering with the oligomerization of the ecto-ATPase protein. Our findings suggest that, under physiological conditions, the gizzard smooth muscle ecto-ATPase may exhibit a range of activities determined by membrane events that affect the status of oligomerization of the enzyme.

Alternative exon-encoded regions of Drosophila myosin heavy chain modulate ATPase rates and actin sliding velocity.

To investigate the molecular functions of the regions encoded by alternative exons from the single Drosophila myosin heavy chain gene, we made the first kinetic measurements of two muscle myosin isoforms that differ in all alternative regions. Myosin was purified from the indirect flight muscles of wild-type and transgenic flies expressing a major embryonic isoform. The in vitro actin sliding velocity on the flight muscle isoform (6.4 microm x s(-1) at 22 degrees C) is among the fastest reported for a type II myosin and was 9-fold faster than with the embryonic isoform. With smooth muscle tropomyosin bound to actin, the actin sliding velocity on the embryonic isoform increased 6-fold, whereas that on the flight muscle myosin slightly decreased. No difference in the step sizes of Drosophila and rabbit skeletal myosins were found using optical tweezers, suggesting that the slower in vitro velocity with the embryonic isoform is due to altered kinetics. Basal ATPase rates for flight muscle myosin are higher than those of embryonic and rabbit myosin. These differences explain why the embryonic myosin cannot functionally substitute in vivo for the native flight muscle isoform, and demonstrate that one or more of the five myosin heavy chain alternative exons must influence Drosophila myosin kinetics.

Management of a diabetic foot ulcer using larval therapy.

Diabetic foot ulcers should be treated to maintain health status, improve quality of life, reduce the number of amputations and lower costs. Many centres that treat diabetic foot ulcers use a multidisciplinary team approach, which comprises medical staff, nurses, podiatrists and an orthotist. At the Manchester Diabetes Centre, larval therapy has been used for several years to debride sloughy diabetic foot ulcers. This case history demonstrates the adverse effects of diabetes on feet, and the multidisciplinary team's contribution to successful treatment and healing of a complex foot lesion.

Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice.

The impact of cancer cachexia and chemotherapy on small intestinal protein metabolism and its subsequent recovery was investigated. Cancer cachexia was induced in mice with colon 26 adenocarcinoma, which is a small and slow-growing tumor characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12ClN3O4S). Both healthy mice and tumor-bearing mice were given a single i.p. injection of cystemustine (20 mg/kg) 3 days after the onset of cachexia. Cancer cachexia led to a reduced in vivo rate of protein synthesis in the small intestine relative to healthy mice (-13 to -34%; P < 0.05), resulting in a 25% loss of protein mass (P < 0.05), and decreased villus width and crypt depth (P < 0.05). In treated mice, acute cytotoxicity of chemotherapy did not promote further wasting of small intestinal protein mass, nor did it result in further damage to intestinal morphology. In contrast, mucosal damage and a 17% reduction in small intestinal protein mass (P < 0.05) were evident in healthy mice treated with cystemustine, suggesting that the effects of chemotherapy on the small intestine in a state of cancer cachexia are not additive, which was an unexpected finding. Complete and rapid recovery of small intestinal protein mass in cured mice resulted from an increase in the rate of protein synthesis compared with healthy mice (23-34%; P < 0.05). Northern hybridizations of mRNA encoding components of the major proteolytic systems suggested that proteolysis may not have mediated intestinal wasting or recovery. A major clinical goal should be to design methods to improve small intestinal protein metabolism before the initiation of chemotherapy.

Developmental components of resting ventilation among high- and low-altitude Andean children and adults.

This paper evaluates the age-associated changes of resting ventilation of 115 high- and low-altitude Aymara subjects, of whom 61 were from the rural Aymara village of Ventilla situated at an average altitude of 4,200 m and 54 from the rural village of Caranavi situated at an average altitude of 900 m. Comparison of the age patterns of resting ventilation suggests the following conclusions: 1) the resting ventilation (ml/kg/min) of high-altitude natives is markedly higher than that of low-altitude natives; 2) the age decline of ventilation is similar in both lowlanders and highlanders, but the starting point and therefore the age decline are much higher at high altitude; 3) the resting ventilation that characterizes high-altitude Andean natives is developmentally expressed in the same manner as it is at low altitude; and 4) the resting ventilation (ml/kg/min) of Aymara high-altitude natives is between 40-80% lower than that of Tibetans.