Results of flap reconstruction: categorisation to reflect outcomes and process in the management of head and neck defects.

The reporting of the outcomes of flap reconstruction is often based on numerical success rates. Whilst this remains a useful variable with which to measure success, it is limited in its ability to reflect the complex processes involved. The lack of consistency in the categorisation of outcomes of flap reconstruction in the head and neck could potentially lead us to lose the opportunity to fully capture the implications of its success or failure, or both. We propose a classification that moves away from primarily reporting the results of its binary nature, and focuses more on the process of reconstruction, particularly in the head and neck.

Do animal exhibitors support and follow recommendations to prevent transmission of variant influenza at agricultural fairs? A survey of animal exhibitor households after a variant influenza virus outbreak in Michigan.

Influenza A viruses circulate in swine and can spread rapidly among swine when housed in close proximity, such as at agricultural fairs. Youth who have close and prolonged contact with influenza-infected swine at agricultural fairs may be at increased risk of acquiring influenza virus infection from swine. Animal and human health officials have issued written measures to minimize influenza transmission at agricultural exhibitions; however, there is little information on the knowledge, attitudes, and practice (KAP) of these measures among animal exhibitors. After an August 2016 outbreak of influenza A(H3N2) variant ("H3N2v") virus infections (i.e., humans infected with swine influenza viruses) in Michigan, we surveyed households of animal exhibitors at eight fairs (including one with known H3N2v infections) to assess their KAP related to variant virus infections and their support for prevention measures. Among 170 households interviewed, most (90%, 151/167) perceived their risk of acquiring influenza from swine to be low or very low. Animal exhibitor households reported high levels of behaviours that put them at increased risk of variant influenza virus infections, including eating or drinking in swine barns (43%, 66/154) and hugging, kissing or snuggling with swine at agricultural fairs (31%, 48/157). Among several recommendations, including limiting the duration of swine exhibits and restricting eating and drinking in the animal barns, the only recommendation supported by a majority of households was the presence of prominent hand-washing stations with a person to monitor hand-washing behaviour (76%, 129/170). This is a unique study of KAP among animal exhibitors and highlights that animal exhibitor households engage in behaviours that could increase their risk of variant virus infections and have low support for currently recommended measures to minimize infection transmission. Further efforts are needed to understand the lack of support for recommended measures and to encourage healthy behaviours at fairs.

Quantum counting: Operator methods for discrete population dynamics with applications to cell division.

The set of natural numbers may be identified with the spectrum of eigenvalues of an operator (quantum counting), and the dynamical equations of populations of discrete, countable items may be formulated using operator methods. These equations take the form of time dependent operator equations, involving Hamiltonian operators, from which the statistical time dependence of population numbers may be determined. The quantum operator method is illustrated by a novel approach to cell population dynamics. This involves Hamiltonians that mimic the process of stimulated cell division. We evaluate two different models, one in which the stimuli are expended in the division process and one in which the stimuli act as true catalysts. While the former model exhibits only bounded cell population variations, the latter exhibits two distinct regimes; one has bounded population fluctuations about a mean level and in the other, the population can undergo growth to levels that are orders of magnitude above threshold levels, through an instability that could be interpreted as a cancerous growth phase.

Micromorts--what is the risk?

The effective communication of risk, which is central to the process of consent, can be difficult, and can be hard for patients to understand. We introduce the potential utility of the micromort, a unit of risk defined as a one-in-a-million chance of sudden death, which allows clinicians to compare the risks of an intervention with those of different activities, making them easier to understand.

Osteotomising the fibular free flap: an anatomical perspective.

Multiple osteotomies with the help of 3-dimensional planning have improved the accuracy of reconstructions, and the reliability and versatility of the fibular free flap is well recognised. To investigate the periosteal blood supply of the fibula and to define safe limits for the size of bony segments, we performed a cadaveric study on 10 fresh frozen lower limbs using a combined barium latex mixture. We modelled cuts at intervals of 1.0, 1.5, and 2.0cm, and assessed the number of periosteal vessels. After virtual dissections using DICOM data obtained from high-resolution computed tomograms (CT), on average we found 12.8 periosteal branches, with a mean (SD) distance between them of 1.36 (0.18)cm. In 34.9% of the 1cm segments there were no visible periosteal vessels. Vascularity seemed to be more reliable in longer segments, with 83.4% of those 1.5cm long, and 94% of those of over 2cm containing at least one branch.

Estimated paediatric mortality associated with influenza virus infections, United States, 2003-2010.

Death certificate reports and laboratory-confirmed influenza deaths probably underestimate paediatric deaths attributable to influenza. Using US mortality data for persons aged <18 years who died during 28 September 2003 to 2 October 2010, we estimated influenza-attributable deaths using a generalized linear regression model based on seasonal covariates, influenza-certified deaths (deaths for which influenza was a reported cause of death), and occurrence during the 2009 pandemic period. Of 32 783 paediatric deaths in the death categories examined, 853 (3%) were influenza-certified. The estimated number of influenza-attributable deaths over the study period was 1·8 [95% confidence interval (CI) 1·3-2·8] times higher than the number of influenza-certified deaths. Influenza-attributable deaths were 2·1 (95% CI 1·5-3·4) times higher than influenza-certified deaths during the non-pandemic period and 1·1 (95% CI 1·0-1·8) times higher during the pandemic. Overall, US paediatric deaths attributable to influenza were almost twice the number reported by death certificate codes in the seasons prior to the 2009 pandemic.

Open wound healing of the osseocutaneous fibula flap donor site.

Split skin grafts are the predominant method of closure for fibular flap donor sites. We present a novel approach to manage the donor site using the inter-related components of secondary intention healing: creation of a lattice to aid partial closure and compression dressings. The technique, which is widely used in dermatological surgery to manage cutaneous defects after operations for skin cancer, avoids the morbidity associated with the use of split skin grafts and enables early postoperative mobilisation.

Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013.

Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n=168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs.

Impact of medical and behavioural factors on influenza-like illness, healthcare-seeking, and antiviral treatment during the 2009 H1N1 pandemic: USA, 2009-2010.

We analysed a cross-sectional telephone survey of U.S. adults to assess the impact of selected characteristics on healthcare-seeking behaviours and treatment practices of people with influenza-like illness (ILI) from September 2009 to March 2010. Of 216,431 respondents, 8.1% reported ILI. After adjusting for selected characteristics, respondents aged 18-64 years with the following factors were more likely to report ILI: a diagnosis of asthma [adjusted odds ratio (aOR) 1.88, 95% CI 1.67-2.13] or heart disease (aOR 1.41, 95% CI 1.17-1.70), being disabled (aOR 1.75, 95% CI 1.57-1.96), and reporting financial barriers to healthcare access (aOR 1.63, 95% CI 1.45-1.82). Similar associations were seen in respondents aged ≥ 65 years. Forty percent of respondents with ILI sought healthcare, and 14% who sought healthcare reported receiving influenza antiviral treatment. Treatment was not more frequent in patients with high-risk conditions, except those aged 18-64 years with heart disease (aOR 1.90, 95% CI 1.03-3.51). Of patients at high risk for influenza complications, self-reported ILI was greater but receipt of antiviral treatment was not, despite guidelines recommending their use in this population.

Evaluation of a non-invasive, inhalational challenge method for rabies vaccine potency assay.

Veterinary rabies vaccines are essential for safeguarding the public from exposure to rabies virus, as vaccination of domestic animals provides a barrier between humans and wildlife reservoirs. Ensuring rabies vaccines are potent and effective is paramount in preventing human exposure to rabies virus. The National Institutes of Health (NIH) test, a mouse vaccination-challenge assay, is the most widely used and internationally recognized assay for potency testing of inactivated rabies vaccines, and it is currently considered the method of choice. In the NIH test, vaccinated mice are challenged by the intracranial (IC) route. The response to the IC challenge can be variable, which often results in invalid tests. In addition, the IC challenge-exposure raises animal welfare concerns. The objective of this study was to evaluate the intranasal route of challenge as a modification to the NIH test to reduce animal pain and suffering until harmonized requirements for in vitro testing of rabies vaccines are developed. Results confirm the intranasal route is an effective route of rabies challenge in mice. However, a valid challenge requires the use of a more concentrated inoculum, in comparison to the intracranial method.

Potency testing of veterinary rabies vaccines: replacement of challenge by in vitro testing: considerations for development of alternative assays.

Vaccination of domestic animals against rabies creates a critical barrier between wildlife reservoirs and the human population. Ensuring these vaccines are potent and effective is paramount in preventing human exposure to this deadly and costly disease. The National Institutes of Health (NIH) test is, at present, the most widely used and internationally recommended potency assay for batch testing inactivated rabies vaccines. This test has numerous inherent limitations and disadvantages, including a lack of precision. The NIH test requires a large number of animals and involves unrelieved pain and suffering. A relevant in vitro assay should provide a more accurate, reproducible, rapid, safe, and humane rabies vaccine potency test.

Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.

Topical ocular antibiotics induce bacterial resistance at extraocular sites.

AIM: To compare the prevalence of antibiotic resistance found in nasopharyngeal Streptococcus pneumoniae between villages treated with topical tetracycline or systemic azithromycin as part of a trachoma control programme. METHODS: All children aged 1-10 years were offered either single dose oral azithromycin treatment (20 mg/kg) or a course of topical 1% tetracycline ointment, depending on the area. Treatment was given annually for 3 years. Six months after the third annual treatment in each village, children were surveyed for nasopharyngeal carriage of S pneumoniae and resistance was determined using broth dilution MIC technique. Children in two additional villages, which had not yet been treated, were also surveyed. RESULTS: Nasopharyngeal carriage of S pneumoniae was similar in the tetracycline treated, azithromycin treated, and untreated areas (p=0.57). However, resistance to tetracycline and azithromycin was distributed differently between the three areas (p=0.004). The village treated with topical tetracycline had a higher prevalence of tetracycline resistance than the other villages (p=0.010), while the oral azithromycin treated village had a higher prevalence of macrolide resistance than the other villages (p=0.014). CONCLUSIONS: Annual mass treatment with oral azithromycin may alter the prevalence of drug resistant S pneumoniae in a community. Surprisingly, topical tetracycline may also increase nasopharyngeal pneumococcal resistance. Topical antibiotics may have an effect on extraocular bacterial resistance.

RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin.

The ORF15 isoform of RPGR (RPGR(ORF15)) and RPGR interacting protein 1 (RPGRIP1) are mutated in a variety of retinal dystrophies but their functions are poorly understood. Here, we show that in cultured mammalian cells both RPGR(ORF15) and RPGRIP1 localize to centrioles. These localizations are resistant to the microtubule destabilizing drug nocodazole and persist throughout the cell cycle. RPGR and RPGRIP1 also co-localize at basal bodies in cells with primary cilia. The C-terminal (C2) domain of RPGR(ORF15) (ORF15(C2)) is highly conserved across 13 mammalian species, suggesting that it is a functionally important domain. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we show that this domain interacts with a 40 kDa shuttling protein nucleophosmin (NPM). The RPGR(ORF15)-NPM interaction was confirmed by (i) yeast two-hybrid analyses; (ii) binding of both recombinant and native HeLa cell NPM to RPGR(ORF15) fusion proteins in vitro; (iii) co-immunoprecipitation of native NPM, RPGR(ORF15) and RPGRIP1 from bovine retinal extracts and of native HeLa cell NPM and transfected RPGR(ORF15) from cultured cells and (iv) co-localization of NPM and RPGR(ORF15) at metaphase centrosomes in cultured cells. NPM is a multifunctional protein chaperone that shuttles between the nucleoli and the cytoplasm and has been associated with licensing of centrosomal division. RPGR and RPGRIP1 join a growing number of centrosomal proteins involved in human disease.

Multistate evaluation of invasive pneumococcal diseases in adults with human immunodeficiency virus infection: serotype and antimicrobial resistance patterns in the United States.

Persons with acquired immunodeficiency syndrome (AIDS) have a higher incidence of invasive pneumococcal disease (IPD) than other adults, and many receive long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylactic therapy. We used 1998-1999 data from the Active Bacterial Core surveillance of the Emerging Infections Program Network to compare IPD infections between adults aged 18-64 years with human immunodeficiency virus (HIV) infection and other adults. Of 2346 patients with IPD, 416 (18%) had HIV or AIDS (HIV/AIDS). Certain serotypes (serotypes 6A, 6B, 9N, 9V, 18C, 19A, 19F, and 23F) were more common among patients with HIV/AIDS than in adults with no underlying disease (P<.05, vs. serotype 4), even when TMP-SMZ-nonsusceptible isolates were excluded. HIV/AIDS (adjusted odds ratio [aOR], 1.93; 95% confidence interval [CI], 1.44-2.59), immunocompromising conditions other than HIV/AIDS (aOR, 1.56; 95% CI, 1.12-2.18), and black race (aOR, 1.50; 95% CI, 1.20-1.88) were independent risk factors for infection with these serotypes. HIV/AIDS was not an independent risk factor for TMP-SMZ nonsusceptibility. Vulnerability to certain serotypes among adults with HIV/AIDS may have implications in prevention strategies.

Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.

Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.

APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box.

Nek2 is a NIMA-related kinase implicated in regulating centrosome structure at the G(2)/M transition. Two splice variants have been identified that exhibit distinct patterns of expression during cell cycle progression and development. Here we show that Nek2A, but not Nek2B, is destroyed upon entry into mitosis coincident with cyclin A destruction and in the presence of an active spindle assembly checkpoint. Destruction of Nek2A is mediated by the proteasome and is dependent upon the APC/C-Cdc20 ubiquitin ligase. Nek2 activity is not required for APC/C activation. Nek2A destruction in early mitosis is regulated by a motif in its extreme C-terminus which bears a striking resemblance to the extended destruction box (D-box) of cyclin A. Complete stabilization of Nek2A requires deletion of this motif and mutation of a KEN-box. Destruction of Nek2A is not inhibited by the cyclin B-type D-box, but the C-terminal domain of Nek2A inhibits destruction of both cyclins A and B. We propose that recognition of substrates by the APC/C-Cdc20 in early mitosis depends upon possession of an extended D-box motif.