From chaos to a new norm: The Birmingham experience of restructuring the largest plastics department in the UK in response to the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic presented unprecedented challenges for healthcare systems worldwide. The Queen Elizabeth Hospital, Birmingham, has one of the largest burns, hands and plastics department in the UK, totalling 83 doctors. Our response to the COVID-19 response was uniquely far reaching, with our department being given responsibility of an entire 36 bed medical COVID-19 ward in addition to our commitment to specialty-specific work, and saw half of our work force re-deployed to Intensive Treatment Unit (ITU). Our aim was to exploit the high calibre of doctors found in plastic surgery, and to demonstrate, we were able to support the COVID-19 effort beyond our normal scope of practice. In order to achieve this aim, the department underwent significant structural and leadership changes. Factors considered included: rota and shift pattern changes to implement depth and resilience to sudden fluctuations in staffing levels; a preparatory phase for focussed upskilling and relevant training packages to be delivered; managing the COVID-19 ward cover and ITU deployment; adjustments to our front of house and elective specialty-specific service, including developing alternative and streamlined patient pathways; mitigating the effects on plastic surgical training during the pandemic; the importance of communications for patient care and physician wellbeing; and leadership techniques and styles we considered important. By sharing our experience during this pandemic, we hope to reflect on and share lessons learned, as well as to demonstrate that it is possible to rapidly mobilise and retrain plastic surgeons at all levels to contribute safely and productively beyond a specialty-specific scope of care.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

Bioactive Constituents from an Endophytic Fungus, Penicillium polonicum NFW9, Associated with Taxus fauna.

BACKGROUND: Endophytic fungi are being recognized as vital and untapped sources of a variety of structurally novel and unique bioactive secondary metabolites in the field of natural products drug discovery. Herein, this study reports the isolation and characterization of secondary metabolites from an endophytic fungus Penicillium polonicum (NFW9) associated with Taxus fuana. METHOD: The extracts of the endophytic fungus cultured on potato dextrose agar were purified using several chromatographic techniques. Biological evaluation was performed based on their abilities to inhibit tumor necrosis factor-alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) and cytotoxicity assays. RESULTS: Bioactivity-directed fractionation of the ethyl acetate extract of a fermentation culture of an endophytic fungus, Penicillium polonicum led to the isolation of a dimeric anthraquinone, (R)- 1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetraone (1), a steroidal furanoid (-)-wortmannolone (2), along with three other compounds (3-4). Moreover, this is the first report on the isolation of compound 1 from an endophytic fungus. All purified metabolites were characterized by NMR and MS data analyses. The stereo structure of compound 1 was determined by the measurement of specific optical rotation and CD spectrum. The relative stereochemistry of 2 was confirmed by single-crystal X-ray diffraction. Compounds 2-3 showed inhibitory activities in the TNF-α-induced NF-κB assay with IC50 values in the range of 0.47-2.11 µM. Compounds 1, 4 and 5 showed moderate inhibition against NF-κB and cancer cell lines. CONCLUSION: The endophytic fungus Penicillium polonicum of Taxus fuana is capable of producing biologically active natural compounds. Our results provide a scientific rationale for further chemical investigations into endophyte-producing natural products, drug discovery and development.

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution. METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/µL) and oIR (CD4 T-cell count > 500 cells/µL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells. RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses. CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

Identification of Natural Infections in Sheep/Goats with HoBi-like Pestiviruses in China.

The natural infections of HoBi-like pestiviruses in cattle have been reported in South America, Europe and Asia. In China, although the detections of HoBi-like pestivirus have been reported, the epidemiological investigation was limited. From January 2014 to October 2015, several flocks of sheep/goats in Henan province in central China suffered respiratory diseases which were recovered slowly after antibiotics treatment. To test whether it is the HoBi-like pestivirus caused this symptom, 49 serum samples and 22 nasal swabs were then collected for analysis by serology and RT-PCR. Serological result revealed that prevalence of pestivirus in small ruminants was 12.2% (6/49) in central China. Sequence analysis of partial 5'-UTR nucleotides of pestivirus-positive samples suggested that HoBi-like pestivirus might have circulated in sheep/goats of China for a period and have evolved into new genotype clusters. It is apparent that the study provides the molecular evidence of natural infections in goat/sheep species with HoBi-like pestiviruses in China.

Whole brain radiation therapy followed by intensity-modulated boosting treatment combined with concomitant temozolomide for brain metastases from non-small-cell lung cancer.

BACKGROUND: Brain metastases (BMs) represent an important cause of morbidity in patients with non-small-cell lung cancer (NSCLC) and are associated with a mean survival of <1 year. Thus, new regimens improving the outcome of these patients are urgently needed. We have evaluated the response to treatment, overall survival, disease progression, and adverse effects of a concomitant treatment with whole brain radiation therapy (WBRT) followed by intensity-modulated boosting RT (IMBRT) and temozolomide (TMZ) in patients with BMs from NSCLC. METHODS: A total of 32 patients with no more than four BMs were enrolled in this retrospective study. Patients received 30 Gy of WBRT in 15 fractions and followed by 20 Gy of IMBRT in 10 fractions with concomitant TMZ of 75 mg/m(2)/day orally during RT and continued TMZ therapy (150-200 mg/m(2)/day for 5 days every 28 days for an additional 2-6 cycles after RT). RESULTS: Three patients had a complete response, 9 patients had a partial response, while 15 patients had stable disease; therefore, the objective responses achieved 37.5 %. Median overall survival was 8.0 months and median time to progression was 5.5 months. Common treatment-related adverse effects (Grade ≤2) included nausea, vomiting, and asthenia. Grade 3 or worse hematologic toxicities were rare. No patient presented with gross neurocognitive dysfunction. CONCLUSION: WBRT followed by IMBRT combined with concomitant TMZ is well tolerated, yielding an encouraging objective response rate; however, overall survival improves slightly comparing with RTOG 9508 randomized trial.

Comparable efficacy and safety of 8 weeks treatment with agomelatine 25-50mg or fluoxetine 20-40mg in Asian out-patients with major depressive disorder.

OBJECTIVE: This randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD). METHOD: Patients were randomly assigned to receive either agomelatine (25-50mg/day, n=314) or fluoxetine (20-40mg/day, n=314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events. RESULTS: Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (-14.8±7.3 and -15.0±8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p=0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population. CONCLUSIONS: Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients.

Predictors of early clinical deterioration after acute ischemic stroke.

The measurements for predicting early deterioration of stroke patients is controversial. We studied laboratory measurements and previously identified risk factors to identify factors or predictors of early deterioration after stroke. A prospective observational study of 196 patients with first-time acute ischemic stroke was performed. Demographic data, patient histories, laboratory measurements, and initial stroke severity assessments were recorded. Patients with early deterioration in National Institutes of Health Stroke Scale scores (increase ≥3 points within 3 days) were defined as having stroke-in-evolution (SIE). Thirty patients were diagnosed with SIE. An initial National Institutes of Health Stroke Scale score of 12 or higher, a Glasgow Coma Scale score of 12 or lower, d-dimers more than 1000, or blood urea nitrogen/creatinine (BUN/Cr) ratio higher than 15 were more frequent in SIE patients. After multivariate analysis, only a BUN/Cr higher than 15 was independent predictor of SIE. These patients were 3.41-fold more likely to have SIE (P = .008). These findings suggest that BUN/Cr may be a novel predictor of SIE, potentially useful in emergency departments.

Identification of Dryopteris crassirhizoma and the adulterant species based on cpDNA rbcL and translated amino acid sequences.

Dry rhizome of Dryopteris crassirhizoma Nakai (Dryopteridaceae), also known as Guan Zhong, is a traditional Chinese herbal medicine used in the treatment of viral disease. But the dry rhizomes of Woodwardia JAPONICA (L. f.) Sm., OSMUNDA JAPONICA Thunb. and Cyrtomium fortunei J. Sm. are also used as Guan Zhong in local areas. The adulterants are similar to Dryopteris crassirhizoma. It is difficult to identify the botanical origin of these herbs. In our study, sequences of the cpDNA RBCL gene were determined and analyzed for Dryopteris crassirhizoma and adulterant species, where nineteen molecular markers had been determined. Also, amino acid sequences translated from the RBCL gene were analyzed and four important molecular markers were detected. Based on cpDNA RBCL and translated amino acid sequences, Dryopteris crassirhizoma can easily be distinguished from the other three fern species.

An assessment survey of anti-tuberculosis drug management in Cambodia.

SETTING: One hundred and seven public health facilities with tuberculosis (TB) service and 66 private pharmacies in 14 provinces. OBJECTIVES: To assess the knowledge, attitudes and practices (KAP) of TB service providers, new smear-positive pulmonary TB out-patients and drug storekeepers, to document practices in the public sector TB drug procurement system, to measure TB drug availability in private pharmacies and to compare public and private sector TB drug prices with international prices. DESIGN: Documents and treatment record reviews, inventory checks and structured interviews. RESULTS: The prescribing practices of the TB service providers were acceptable. The level of new smear-positive TB out-patients' knowledge of TB treatment was high. The storekeepers' inventory practices for TB drugs indicated a need for improvement. Various TB drugs were available in the private pharmacies. TB drug prices in the public sector were similar to international reference prices, although they were higher than the Global TB Drug Facility prices. CONCLUSIONS: An indicator-based anti-tuberculosis drug management assessment survey can measure the current situation and quality of DOTS, identify any weaknesses or changes in practice from the norm, and simultaneously serve as a basis for training of TB service providers and storekeepers.

Electrical induction of ventricular fibrillation for resuscitation from postcountershock pulseless and asystolic cardiac arrests.

BACKGROUND: There is increasing evidence that defibrillation from prolonged ventricular fibrillation (VF) before CPR decreases survival. It remains unclear, however, whether harmful effects are due primarily to initial countershock of ischemic myocardium or to resultant postdefibrillation rhythms (ie, pulseless electrical activity [PEA] or asystole). METHODS AND RESULTS: We induced 15 dogs into 12 minutes of VF and randomized them to 3 groups. Group 1 was defibrillated at 12 minutes and then administered advanced cardiac life support (ACLS); group 2 was allowed to remain in VF and was subsequently defibrillated after 4 minutes of ACLS; group 3 was defibrillated at 12 minutes, electrically refibrillated, and then defibrillated after 4 minutes of ACLS. All group 1 and 3 animals were defibrillated into PEA/asystole at 12 minutes. After 4 minutes of ACLS, group 2 and 3 animals were effectively defibrillated into sinus rhythm. The extension of VF in group 2 and 3 subjects paradoxically resulted in shorter mean resuscitation times (251+/-15 and 245+/-7 seconds, respectively, versus 459+/-66 seconds for group 1; P<0.05) and improved 1-hour survival (10 of 10 group 2 and 3 dogs versus 1 of 5 group 1 dogs; Fisher's exact, P<0.005) compared with more conservatively managed group 1 subjects. CONCLUSIONS: Precountershock CPR during VF appears more conducive to resuscitation than CPR during postcountershock PEA or asystole. The intentional induction of VF may prove useful in the management of PEA and asystolic arrests.

Lead configuration for defibrillator implantation in a patient with congenital heart disease and a mechanical prosthetic tricuspid valve.

The authors devised a nonthoracotomy defibrillation system for a patient with a prosthetic tricuspid valve using existing technology and previously established implantation techniques. Their lead configuration deviates substantially from existing designs in its primary use of a coronary sinus defibrillation coil and a left-sided subcutaneous array to distribute current across the ventricular myocardium.

DNA binding mediated by the wheat HMGa protein: a novel instance of selectivity against alternating GC sequence.

The high-mobility-group (HMG) chromosomal protein wheat HMGa was purified to homogeneity and tested for its binding characteristics to double-stranded DNA. Wheat HMGa was able to bind to P268, an A/T-rich fragment derived from the pea plastocyanin gene promoter, producing a small mobility shift in gel retardation assays where the bound complex was sensitive to addition of proteinase K but resistant to heat treatment of the protein, consistent with the identity of wheat HMGa as a putative HMG-I/Y protein. Gel retardation assays and southwestern hybridization analysis revealed that wheat HMGa could selectively interact with the DNA polynucleotides poly(dA).poly(dT), poly(dAdT).poly(dAdT), and poly(dG).poly(dC), but not with poly(dGdC).poly(dGdC). Surface plasmon resonance analysis determined the kinetic and affinity constants of sensor chip-immobilized wheat HMGa for double-stranded DNA 10-mers, revealing a good affinity of the protein for various dinucleotide combinations, except that of alternating GC sequence. Thus contrary to prior reports of a selectivity of wheat HMGa for A/T-rich DNA, the protein appears to be able to interact with sequences containing guanine and cytosine residues as well, except where G/C residues alternate directly in the primary sequence.

Cardiopulmonary resuscitation with a hydraulic-pneumatic band.

Improved blood flow during cardiopulmonary resuscitation (CPR) has been shown to enhance survival from cardiac arrest. Chest compression with a circumferential pneumatic vest enhances blood flow, but the size, weight, and energy consumption of the inflation system limit its portability and, thereby, have made clinical studies difficult. The purpose of this investigation was to study an improved circumferential chest compression device that uses a constricting band that is pneumatically actuated. The constricting band applies its force to a hydraulic cushion that contacts the anterior and lateral aspects of the chest. The hydraulic cushion transfers the circumferential constriction to inward force. CPR was performed on subjects 5 mins after induction of ventricular fibrillation, with the hydraulic-pneumatic band system (HB-CPR), with a pneumatic vest system (PV-CPR), and with standard manual CPR (S-CPR), each done for 2 mins in randomized order. Aortic and right atrial pressures were measured with micromanometers. Coronary perfusion pressure was calculated as the mean difference between the aortic and right atrial pressures during the release phase of chest compression. Aortic pressure and coronary perfusion pressure with HB-CPR and PV-CPR were improved over S-CPR, and HB-CPR produced comparable pressures to those of PV-CPR. The system for performing HB-CPR, however, was substantially lighter (10 vs. 50 kg) and consumed less energy (300 vs. 1000 watts) than that for PV-CPR. Thus, HB-CPR appears to produce a similar improvement in hemodynamics over S-CPR as PV-CPR but may be more portable than PV-CPR. Therefore, HB-CPR may allow larger scale testing of circumferential chest compression approaches.

Resuscitation after prolonged ventricular fibrillation with use of monophasic and biphasic waveform pulses for external defibrillation.

BACKGROUND: Survival after prolonged ventricular fibrillation (VF) appears severely limited by 2 major factors: (1) low defibrillation success rates and (2) persistent post-countershock myocardial dysfunction. Biphasic (BP) waveforms may prove capable of favorably modifying these limitations. However, they have not been rigorously tested against monophasic (MP) waveforms in clinical models of external defibrillation, particularly where rescue from prolonged VF is the general rule. METHODS AND RESULTS: We randomized 26 dogs to external countershocks with either MP or BP waveforms. Hemodynamics were assessed after shocks applied during sinus rhythm, after brief VF (>10 seconds), and after resuscitation from prolonged VF (>10 minutes). Short-term differences in percent change in left ventricular +dP/dt(max) (MP -16+/-28%, BP +9.1+/-24%; P=0.03) and left ventricular -dP/dt(max) (MP -37+/-26%, BP -18+/-20%; P=0.05) were present after rescue from brief VF, with BP animals exhibiting less countershock-induced dysfunction. After prolonged VF, the BP group had lower mean defibrillation thresholds (107+/-57 versus 172+/-88 J for MP, P=0.04) and significantly shorter resuscitation times (397+/-73.7 versus 488+/-74.3 seconds for MP, P=0.03). CONCLUSIONS: External defibrillation is more efficacious with BP countershocks than with MP countershocks. The lower defibrillation thresholds and shorter resuscitation times associated with BP waveform defibrillation may improve survival after prolonged VF arrest.

Anaesthesia and juvenile Huntington's disease.

Juvenile Huntington's Disease (JHD) is an involuntary movement disorder that comprises both neurological and psychiatric symptoms. Whilst it has many similarities to Huntington's Disease, it is regarded as a separate clinical entity. The anaesthetic plan should be based on careful assessment of the important issues, including the risk of regurgitation and pulmonary aspiration, possible associated autonomic neuropathy, poor respiratory function and the avoidance of precipitating convulsions and clonic spasms. We describe the management of a 12-year-old girl with JHD scheduled for gastroscopy under general anaesthesia necessitating the use of suxamethonium. We suggest an alternative mechanism for the delayed recovery seen in our patient and in other adult case reports.

Ultrastructural study of upper surface layer in rat articular cartilage by "in vivo cryotechnique" combined with various treatments.

The ultrastructures of the upper surface layer of rat articular cartilage were studied with our "in vivo cryotechnique" followed by freeze-substitution method for scanning electron microscopy (SEM) or transmission electron microscopy (TEM). Rat hip or knee articular cartilage was quickly frozen by the in vivo cryotechnique with liquid isopentane-propane cryogen (-193 degrees C), and surface areas of some frozen specimens were freeze-fractured with a scalpel in liquid nitrogen. They were freeze-substituted and freeze-dried, ion-sputtered, and then observed in SEM. Other frozen specimens were routinely freeze-substituted and embedded in epoxy resin for TEM. Many globular structures were detected in the thick upper surface layer that had not been revealed by the conventional fixation methods. Their sizes were reduced by Triton X-100 treatment, and their localization was also detected in synovial fluid, as revealed by SEM. Such globular lipid-like structures in the upper surface layer of hip or knee articular cartilage might contribute to joint lubrication.