Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

The Development of a National Paediatric Psycho-Oncology Service.

Aims To investigate the psychological care provided to children and young adolescents with cancer and their families within the National Children's Cancer Service (NCCS), Ireland, in respect of the national and international standards of care. Methods A retrospective audit of 316 referrals made over 32 months by the NCCS to the psychology service in malignant haematology and oncology was performed. Results The audit revealed that out of 316 patients, a yearly average of 189 (50%) of urgently referred patients received psychological support within the NCCS between January 2013 and August 2016. Furthermore only 20 (22%) undergoing haematopoietic stem cell transplantation (HSCT), 14 (22%) referred to the paediatric palliative care team, and 84 (62%) of teenage patients received psychological input during this timeframe. Conclusion The audit revealed that the current psychology service provision is failing to meet the international standards of care. Due to the data provided by this audit, in conjunction with a clinical risk assessment of the service, funds for the post of principal psychologist have been secured. Further psychology posts (HSCT, late-effects and neuropsychology), and development of the psycho-oncology model of care are required to ensure equality of access and evidence-based psychological care for all children with cancer.

Burkitt Lymphoma/Leukaemia in Children & Young Adolescents.

Aims Burkitt Lymphoma (BL) accounts for approximately 40% of childhood non-Hodgkin Lymphoma (NHL) in the developed world. Survival rates have improved dramatically in recent years, a success attributed to better use of poly-chemotherapy and targeted immunotherapy. Nevertheless, relapse is unpredictable and carries a dismal prognosis. We report on event-free survival (EFS) and overall survival (OS) rates in the Republic of Ireland (ROI) during 2000-2017, and evaluate novel predictors of outcome. Methods Data was collected by retrospective review of patient medical records. Results Thirty-three patients were identified (twenty-five [76%] males, eight [24%] females), fourteen [42%] having stage III disease at presentation. Six [18%] had stage IV disease. Five [15%] had refractory disease; one salvaged with allogeneic stem cell transplantation. Of the four [12%] who died; two [50%] had weights >99th centile, one [25%] >90th centile. One died during induction from refractory lactic acidosis, one from early relapse. Discussion EFS and OS was 85% and 89% respectively; in keeping with the best international standards. Obesity appears to be a poor predictor of outcome in our cohort.

Evaluation of light colour manipulation on physiological response and growth performance of broiler chickens.

Artificial illumination, including light quality, is crucial in modern broiler management. The aim of this study was to examine the effect of a switch in light colour on the performance of broiler chickens in tropical environments. A total of 280 1-day-old Arbor acre male chicks were used for this study and were weighed and assigned to different light environments viz. white (WH), green (GR), blue (BL), GR switched to BL at 14 days (GB), BL switched to GR at 14 days (BG), BL switched to GR at 28 days (BGG) and GR switched to BL at 28 days (GBB) having four replicates of ten birds each. Body weight, weight gain, feed intake and feed conversion ratio were recorded weekly. Blood samples were collected from 2 birds per replicate weekly for the determination of plasma triiodothyronine (T3), haematology and serum biochemical parameters. The experiment was laid out in a completely randomised design. Results showed that the final body weights of the birds in GBB and GB were comparable but higher than those of the other treatment groups. Feed intake of the chickens in WH was similar to that of BG but higher than those of the other treatment groups, while FCR of the birds in WH was higher (P < 0.05) than the other treatment groups. Plasma T3 of the birds in GR was comparable to that of birds in BL but significantly higher than those of the birds in WH and a similar trend was also observed at weeks 1 and 2. Heterophil/lymphocyte ratio (H/L) of the birds in WH was significantly higher than those of BL and GR whose values were similar to those in GB and BG. Heterophil/lymphocytes of the birds in WH was higher than those of BG, GR, BGG, GB and GBB but similar to those of BL. The breast muscle of the birds in GBB and GB was similar to those of BGG and GR and significantly higher than those of WH, BL and BG. Based on the results obtained in this study, it was concluded that the use of green light up to 28 days in combination with blue light stimulated the growth of broiler chickens and manipulation of light colours can be used to improve the welfare and performance of chickens.

Development of the central nervous system in equine twin fetuses derived by somatic cell nuclear transfer.

Because of the growing importance of horses in leisure and several sports, somatic cell nuclear transfer (SCNT) is being used more frequently for cloning animals for performance and reproductive purposes. However, because of the need to perforate the zona pellucida during microsurgical reconstruction of the oocyte, it is possible that SCNT-derived embryos undergo premature hatching, resulting in embryo bisection and twinning. Therefore, because equine twin pregnancies often lead to abnormal embryo development and pregnancy failure, we performed a detailed comparative assessment of equine twin fetuses derived by SCNT with particular attention on the development of the central nervous system at 40 and 60 days gestation. The results of this study indicate that although cloned twin embryos show small differences in size, they do not exhibit apparent macro- or microscopic developmental discrepancies in the central nervous system, suggesting that the twining phenomenon resulting from SCNT does not affect fetal differentiation.

Phosphonic Acids for Interfacial Engineering of Transparent Conductive Oxides.

Transparent conducting oxides (TCOs), such as indium tin oxide and zinc oxide, play an important role as electrode materials in organic-semiconductor devices. The properties of the inorganic-organic interface-the offset between the TCO Fermi level and the relevant transport level, the extent to which the organic semiconductor can wet the oxide surface, and the influence of the surface on semiconductor morphology-significantly affect device performance. This review surveys the literature on TCO modification with phosphonic acids (PAs), which has increasingly been used to engineer these interfacial properties. The first part outlines the relevance of TCO surface modification to organic electronics, surveys methods for the synthesis of PAs, discusses the modes by which they can bind to TCO surfaces, and compares PAs to alternative organic surface modifiers. The next section discusses methods of PA monolayer deposition, the kinetics of monolayer formation, and structural evidence regarding molecular orientation on TCOs. The next sections discuss TCO work-function modification using PAs, tuning of TCO surface energy using PAs, and initiation of polymerizations from TCO-tethered PAs. Finally, studies that examine the use of PA-modified TCOs in organic light-emitting diodes and organic photovoltaics are compared.

Neonatal brain injury and systemic inflammation: modulation by activated protein C ex vivo.

Infection and inflammation can be antecedents of neonatal encephalopathy (NE) and increase the risk of neurological sequelae. Activated protein C (APC) has anti-coagulant and anti-inflammatory effects and provides neuroprotection in brain and spinal cord injury. We examined neutrophil and monocyte responses to lipopolysaccharide (LPS) in infants with NE compared with healthy adult and neonatal controls, and also studied the effect of APC. Whole blood was incubated with LPS and APC and Toll-like receptor (TLR)-4 (LPS recognition), CD11b expression (activation) and intracellular reactive oxygen intermediate (ROI; function) release from neutrophils and monocytes was examined by flow cytometry serially from days 1 to 7. We found a significant increase in neutrophil ROI in infants with NE on day 3 following LPS compared to neonatal controls and this augmented response was reduced significantly by APC. Neutrophil and monocyte CD11b expression was increased significantly on day 1 in infants with NE compared to neonatal controls. LPS-induced neutrophil TLR-4 expression was increased significantly in infants with NE on days 3 and 7 and was reduced by APC. LPS-induced monocyte TLR-4 was increased significantly in infants with NE on day 7. Neutrophil and monocyte activation and production of ROIs may mediate tissue damage in infants with NE. APC modified LPS responses in infants with NE. APC may reduce the inflammatory responses in NE and may ameliorate multi-organ dysfunction. Further study of the immunomodulatory effects of protein C may be warranted using mutant forms with decreased bleeding potential.

Sickle cell disease: time for a targeted neonatal screening programme.

Ireland has seen a steady increase in paediatric sickle cell disease (SCD). In 2005, only 25% of children with SCD were referred to the haemoglobinopathy service in their first year. A non-funded screening programme was implemented. This review aimed to assess the impact screening has had. All children referred to the haemoglobinopathy service born in Ireland after 2005 were identified. Data was collected from the medical chart and laboratory system. Information was analysed using Microsoft Excel. 77 children with SCD were identified. The median age at antibiotic commencement in the screened group was 56 days compared with 447 days in the unscreened group, p = < 0.0003. 22 (28%) of infants were born in centre's that do not screen and 17 (81%) were over 6 months old at referral, compared with 14 (21%) in the screened group. 6 (27%) of those in the unscreened group presented in acute crisis compared with 2 (3%) in the screened population. The point prevalence of SCD in Ireland is 0.2% in children under 15 yr of African and Asian descent. We identified delays in referral and treatment, which reflect the lack of government funded support and policy. We suggest all maternity units commence screening for newborns at risk of SCD. It is a cost effective intervention with a number needed to screen of just 4 to prevent a potentially fatal crisis.

Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center.

BACKGROUND: Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death. METHODS AND RESULTS: We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Children's Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirty-one (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11; P<0.001). ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1; P=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8; P=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died. CONCLUSIONS: Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death.

Novel insights into patient's thoughts about their body image in abdominal wall hernia.

BACKGROUND: Abdominal wall hernias (AWH) are frequently large and deforming. Despite this, little is known about how AWH impact upon body image. This study is the first study to qualitatively examine patients' subjective lived experiences of how AWH affects their body image. METHODS: Fifteen patients were interviewed from a purposive sample of AWH patients awaiting surgery until no new narrative themes emerged. Interviews explored patient thoughts and experiences of AWH and body image. Data were examined using interpretative phenomenological analysis (IPA). RESULTS: Two key themes pertaining to body image were identified: "Changes to perceptions of self" and "Fears concerning other's perceptions of them". Both themes were often interrelated and displayed detrimental effects AWH had on patients' body image. CONCLUSIONS: Our findings illustrate that AWH detrimentally affected patients' body image. This aspect of patient care can be treated and managed through better pre-operative information, including on body image as part of a holistic needs assessment (HNA), and ensuring the results are addressed in a patient care package. These development suggestions may positively affect the AWH patient's experience and outcomes in terms of Quality of Life (QoL) by preparing patients better for realistic results regarding what can be achieved in terms of form, function thus making a more holistic recovery from surgery.

Altered central pain processing after pancreatic surgery for chronic pancreatitis.

BACKGROUND: Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. METHODS: Patients with CP underwent quantitative sensory testing. Pain processing was measured via electrical pain detection (ePDT) and electrical pain tolerance (ePTT) thresholds in dermatomes C5 and L4. Inhibitory descending pain control mechanisms were assessed using the conditioned pain modulation (CPM) paradigm. Healthy controls and patients with CP were compared, and patients with CP and a poor pain outcome (visual analogue scale (VAS) score greater than 30) were compared with those with a good pain outcome (VAS score 30 or less). RESULTS: Forty-eight patients with CP had lower ePDT, ePTT and CPM responses compared with values in 15 healthy controls (P < 0·030). The sum of ePDT values was lower in patients with a poor pain outcome than in those with a good outcome (median 7·1 versus 11·2 mA; P = 0·008). There was a correlation with the VAS score and the sum of ePDT values (rs = -0·45, P = 0·016) and ePTT values (rs = -0·46, P = 0·011), and CPM response (rs = -0·43, P = 0·006) in patients with CP. CONCLUSION: After pain-relieving pancreatic surgery, patients with CP exhibit altered central pain processing compared with that in healthy controls. Poor pain outcomes are associated with more central sensitization and more pronociceptive descending pain modulation, and this should be considered when managing persistent pain after pain-relieving surgery for CP.

Circulating pro- and anticoagulant levels in normal and complicated primigravid pregnancies and their relationship to placental pathology.

We aimed to compare the changes in factor VIII:C, antithrombin, protein C, protein S and fibrinogen in a cohort of low-risk primigravida who developed maternal or fetal complications to those who had uncomplicated pregnancies and to correlate these findings with placental pathology. This is a case-control study of 170 cases and 122 controls selected from a prospective cohort of 1,011 low-risk primigravida. Significantly elevated levels of factor VIII:C and significantly decreased levels of antithrombin were seen in women who developed pre-eclampsia (p <0.001), placental infarction (p < 0.001) or had infants with a birth weight < 3rd centile (p < 0.001). Placental villous dysmaturity was significantly associated with raised factor VIII:C (p < 0.001). Women who developed pre-eclampsia showed elevated fibrinogen at 14 weeks (p = 0.03). Significantly higher than normal pregnancy levels of factor VIII:C, in tandem with significantly lower antithrombin levels associated with certain adverse pregnancy outcomes, may be related to underlying placental insufficiency. This is supported by associated placental findings.

Haemoglobin variants among voluntary blood donors in Jos, Nigeria: the implications on blood transfusion.

INTRODUCTION: The normal haemoglobin is an efficient transporter of oxygen to the tissues and carbondioxide from tissues to the lungs for elimination. Various abnormal haemoglobin variants including, the sickle cell diseases, have been described with varying sickling tendencies. AIMS: This study aimed to determine the haemoglobin variants among voluntary blood donors in Jos. METHOD: Records of the age, sex, Haemoglobin level, and the haemoglobin genotype of all voluntary blood donors who donated blood at the National Blood Transfusion Service Centre, Jos, Nigeria between January 2011 and April 2012; and their haemoglobin levels and protein electrophoresis determined, were reviewed. RESULTS: A total of 937 blood donors, 658 (70.23%) males and 279 (29.79%) females, mean age 32.4 years, donated blood voluntarily, their haemoglobin electrophoretic patterns determined by alkaline cellulose acetate electrophoresis. Donor blood haemoglobin levels were determined by automation. Haemoglobin protein electrophoretic patterns identified among our donors were 77.70% AA, 21.88% AS, 0.22% SC, 0.11% AC and 0.11% SS. Mean haemoglobin levels of the donors according to their haemoglobin proteins electrophoretic patterns were, 150.4 +/- 12.5 gms/l for AA, 151.9 +/- 13.8 gms/l for AS and 131.1 +/- 5.0 gms/l for haemoglobin SC. CONCLUSION: Determination of haemoglobin protein electrophoretic patterns of blood unit for transfusion could enhance selective blood issuing based on recipient's haemoglobin type.

Abdominal wall hernia and mental health: patients lived experiences and implications for patient care.

BACKGROUND: Abdominal wall hernia (AWH) affects mental health and mental health questions are frequently included within Patient-Reported Outcome Measures (PROMS) for this patient population. However, these questions have not been informed by the subjective lived experiences of mental health in AWH patients. This study is the first to qualitatively examine how AWH affects patients' mental health. METHODS: Fifteen patients were interviewed from a purposive sample of AWH patients until no new themes emerged. Interviews explored patient thoughts and experiences of AWH and mental health. Data were examined using Interpretative Phenomenological Analysis (IPA). RESULTS: Three key themes pertaining to mental health were identified: "psychological and emotional distress", "identity disruption" and "coping mechanisms and support systems". CONCLUSION: Our findings illustrate that AWH is a pathology that can have a significant detrimental impact on people's mental health. This impact has implications for patient care and can be treated and managed through better psychological support. This support may positively affect AWH patient's experience and outcomes in terms of quality of life. This paper provides recommendations for improved AWH patient care in regard to mental health.

Role of induced negative and positive emotions in sensitivity to itch and pain in women.

BACKGROUND: Itch and pain are common symptoms in skin disease. It has been suggested that negative emotions may play a role in itch and pain. To date, however, the role of emotions has only been studied for pain in experimental studies, not yet for itch. OBJECTIVES: To investigate the effects of negative and positive emotions on the sensitivity to itch and pain. METHODS: Film fragments were used to induce a negative or positive emotional state in healthy women. Itch and pain were induced using the following somatosensory stimuli: electrical stimulation, histamine iontophoresis and the cold pressor test. RESULTS: Results showed that the scores for itch and pain evoked by histamine and the cold pressor test, respectively, were significantly higher in the negative than in the positive emotion condition, whereas tolerance thresholds to electrical stimulation and the cold pressor test, and stimulus unpleasantness scores did not differ between the two conditions. CONCLUSIONS: These findings for the first time indicate in an experimental design that emotions play a role in sensitivity to somatosensory sensations of both itch and pain.

Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.

BACKGROUND: Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments T5-T12 and which innervate the vasculature of the liver, pancreas, and the adrenal gland. The purpose of this study was to assess whether and how BTS affects sympathetic noradrenergic and adrenomedullary function in patients with chronic pancreatitis. METHODS: Sixteen patients with chronic pancreatitis for at least 1 year underwent autonomic function testing before and 6 weeks after BTS for intractable pain. Testing was performed during supine rest and during sympathetic stimulation when standing. RESULTS: Supine and standing systolic and diastolic blood pressure were significantly lower post-BTS compared with pre-BTS (P = 0.001). One patient showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels and plasma norepinephrine responses to sympathetic activation during standing were not reduced by BTS. In contrast, supine plasma epinephrine levels and responses during standing were significantly reduced (P < 0.001). Parasympathetic activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E difference, and ΔHRmax. CONCLUSIONS: BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy.

The effect of addition of pregabalin and s-ketamine to local infiltration analgesia on the knee function outcome after total knee arthroplasty.

Pain reduction is important for early mobilization after total knee arthroplasy. Recent studies show that local infiltration analgesia and addition of anti-hyperalgesic drugs (pregabalin and s-ketamine) may improve postoperative analgesia and mobilization. This pilot study was meant to evaluate if this new method of analgesia might improve patients' ability to exercise in the first postoperative days. The secondary goal was to determine what side effects could be expected by using this drug combination. A pilot study showed that patients achieved knee flexion of 88.5 degrees (SD 9.6) already on the second postoperative day. The side effects were mild and mostly self-limiting.

Paediatric umbilical cord blood transplantation.

Umbilical cord blood is being used increasingly as a source of haematopoietic stem cells for transplantation because of rapid availability, and the unavailability of a HLA matched adult donor for some patients. This study reports the characteristics and outcomes of 15 patients who have undergone umbilical cord blood transplantation (UCBT) in Ireland between 1998 and 2009. The median total nucleated cell and CD34+ doses post-processing were 6.5 x 107cells/kg and 1.8 x 105 cells/kg, respectively. Median neutrophil recovery time was 30 days (range, 14-44). Median platelet recovery time was 46.5 days (range, 35-148). 33.3% of patients developed acute cutaneous graft-versus-host disease (GVHD) grade I-II. Three patients died of transplant-related toxicity and two died of leukaemic relapse. We conclude that, with a satisfactory stem cell dose, UCBT offers a high chance of engraftment with acceptable toxicity, and should be regarded as a favourable option in selected patients when satisfactory bone marrow or peripheral blood stem cell donors are not available.

Health-related quality of life in abdominal wall hernia: let's ask patients what matters to them?

INTRODUCTION: Quality of Life (QoL) is an important consideration in patients with abdominal wall hernia (AWH). What matters to patients and their everyday experience living with AWH may depend on a variety of personal, psychological, social and environmental factors. At present, no study has addressed what is important to this particular group of patients by asking the patients themselves. This study aims to determine QoL from the patient's perspective by examining the lived experience in this patient population. METHODS: We interviewed 15 patients with AWH until thematic saturation. The patients were purposively sampled from AWH clinic between February 2020 and June 2020 using topic guides and interview schedules. Verbatim interview transcripts were coded and analysed using NVivo12 software and Interpretative Phenomenological Analysis (IPA). We adhered to consolidated criteria for reporting qualitative research (COREQ). RESULTS: Fifteen participants (8 men and 7 women) of age range 36-85 years, median 65 years, covering all Ventral Hernia Working Group (VHWG) grades. Five superordinate themes were identified each with several subordinate themes, as follows: (1) body image (subthemes-'changes to perceptions of self' and 'fears concerning perceptions of others'). (2) Mental health (subthemes-'emotional responses', 'disruptions to previously solid aspects of identity', 'developing coping strategies'). (3) Symptoms (subthemes-'managing pain', 'freedom of movement', 'restriction and adaptation of function'). (4) Interpersonal relationships (subthemes-'difficulties socially connecting' and 'changes in sexual relations'). (5) Employment (subthemes-'financial pressure', 'return to work issues' and 'costs to family'). CONCLUSION: This is the first phenomenological qualitative study in the field of AWH and presents a rich account of what is important to these patients in terms of QoL. Developed from the patients' own words, the themes are interrelated and should shape our understanding of patients with AWH. This study provides qualitative examples of each theme. This study has identified new themes (body image, interpersonal relationships and employment) that are not incorporated in existing AWH-specific QoL instruments. This is important for surgeons because the study suggests that we are currently not capturing all data relevant to QoL in this specific patient group with current tools. The wider impact of this would be to help counsel patients and support them more holistically through the disease process and it's management. Further research is needed to generate a standardised AWH QoL instrument which incorporates bio-psycho-emotional-social themes important to patients, as identified by patients.