Quality of Life of People Living with HIV in Australia: The Role of Stigma, Social Disconnection and Mental Health.

HIV is a manageable chronic illness, due to advances in biomedical management. However, many people living with HIV (PLHIV) continue to experience psychosocial challenges, which have been associated with poorer quality of life (QoL). This study aimed to explore how psychosocial factors contributed to the QoL of PLHIV in Australia; specifically, the relationship between HIV-related stigma, social connectedness, mental health, and QoL. Participants were 122 PLHIV attending The Albion Centre (a tertiary HIV clinic in Sydney, Australia), who completed questionnaires which measured HIV-related stigma, social support, mental health symptomology and QoL. Results indicated that HIV-related stigma predicted poorer QoL, as did mental health symptomology. Conversely, social connectedness improved QoL. Additionally, social connectedness was found to mediate the relationship between HIV-related stigma and QoL, whereas the hypothesized moderating role of mental health symptomology on this model was not significant. These findings provide insight into the impact of psychosocial factors on QoL, offering practitioners various points of clinical intervention.

TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia.

PURPOSE: Cryofibrinogenemia is a rare cryopathy presenting as acrocyanosis following exposure to cold. Familial presentation has been described but the underlying molecular cause remained undetermined. METHODS: Forty (40) members from a large family with an initial diagnosis of familial cryofibrinogenemia were interviewed and examined to determine affected status and collect DNA. Exome sequencing was performed on three affected individuals from distinct branches of the pedigree. RESULTS: Seventeen (17) family members reported a history of acrocyanosis with cold exposure. None reported symptoms were suggestive of lupus. Exome sequencing of three subjects identified the heterozygous mutation D18N in the TREX1 gene which was then confirmed by Sanger sequencing in all affected as well as 2 unaffected family members. The mutation is already being associated with familial chilblain lupus erythematosus (CHLE), and a systematic review of literature was undertaken to compare reports of familial CHLE and cryofibrinogenemia. Both entities were found to share highly similar clinical presentations suggesting they are part of a same syndrome in which cryofibrinogenemia and lupus manifestations have variable penetrance. CONCLUSIONS: Familial cryofibrinogenemia without lupus should be added to the spectrum of TREX1-related disease.

Standard method for deposition of dry, aerosolized, silica-coated Bacillus spores onto inanimate surfaces.

AIMS: To evaluate a standard aerosolization method for uniformly depositing threat-representative spores onto surfaces. METHODS AND RESULTS: Lyophilized Bacillus anthracis ΔSterne spores, coated in silica, were aerosolized into a containment chamber and deposited onto nine surface types by two independent laboratories. Laboratory A produced a mean loading concentration of 1·78 × 10(5) CFU cm(-2) ; coefficient of variation (CV) was <40% for 96% of samples. Laboratory B produced a mean loading concentration of 7·82 × 10(6) CFU cm(-2) ; 68% of samples demonstrated CV <40%. CONCLUSIONS: This method has been shown to meet the goal of loading threat-representative spores onto surfaces with low variability at concentrations relevant to the Department of Defense. SIGNIFICANCE AND IMPACT OF THE STUDY: As demonstrated in 2001, a biological attack using anthrax disseminated as a dry powder is a credible threat. This method will provide a means to load spores onto surfaces that mimic a 'real-world' scenario of an aerosolized anthrax attack. The method has utility for evaluating sporicidal technologies and for nondecontamination studies, for example fate and transport or reaerosolization.

'What doesn't kill you. . .': A qualitative analysis of factors impacting the quality of life of people living with HIV.

Despite viral suppression, people living with HIV (PLHIV) report lower quality of life (QoL) than the general population, negatively impacting treatment adherence and wellbeing. This qualitative study explored factors influencing QoL of PLHIV. Participants completed a QoL questionnaire, with cut-off scores used to allocate participants into Low-Moderate QoL (n = 11) or High-Very High QoL (n = 10) focus groups. Thematic analysis indicated convergence across factors perceived to impact QoL, with some notable discrepancies. Socioeconomic stability, social connection and support, maintaining good health, adaptive attitudes and reduced impact of stigma were perceived to improve QoL, while obstacles to connection, ageing and poor HIV literacy in the general population were perceived to worsen QoL in both groups. The Low-Moderate QoL group alone identified socioeconomic stressors and ongoing burden of negative life experiences worsened their QoL. Results are presented in the context of local and global HIV health strategies, with implications for clinical management noted.

Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.

We sought to identify the molecular basis of the autosomal dominant form of Kufs disease, an adult onset form of neuronal ceroid lipofuscinosis. We used a combination of classic linkage analysis and Next Generation Sequencing to map and identify mutations in DNAJC5 in a total of three families. We analyzed the clinical manifestations in 20 individuals with mutation in DNAJC5. We report here the mapping and the identification of a p.L116del mutation in DNAJC5 segregating with the disease in two distinct American families, as well as a p.L115R mutation in an additional family. The age of onset and clinical manifestations were very homogeneous among mutation positive individuals, including generalized tonic-clonic seizures, myoclonus, ataxia, speech deterioration, dementia, and premature death. A few individuals also exhibited parkinsonism. DNAJC5, which encodes the cysteine string protein (CSPα), a presynaptic protein implicated in neurodegeneration, causes autosomal dominant Kufs disease. The leucine residues at positions 115 and 116 are hotspots for mutations and result in a homogeneous phenotype of progressive myoclonus epilepsy with onset around 30 years old.

Short-lived noble gas effluent trends from a research reactor.

An understanding of anthropogenic sources of radioactive noble gases in the atmosphere is needed to enhance the discrimination ability of the International Monitoring System's sensors. These sources include commercial and research nuclear reactors and medical isotope production facilities. While abiding by local environmental ordinances these facilities all emit noble gas radioisotopes through normal operation. This research presents measurements and analysis of noble gas isotopes (41Ar, 135Xe, 135mXe, 137Xe, 138Xe, 87Kr, 88Kr, and 89Kr) made directly at the stack of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory. The Xe and Kr noble gases are concurrently observed with 41Ar, a neutron activation product, when the reactor is operational. The magnitude of the Xe and Kr noble gases released is not constant over the HFIR cycle, but they temporally match the 41Ar trend. An isotope activity ratio analysis of these shorter lived isotopes combined with the observation of the cycle's temporal trend helps understand the noble gas production mechanism at the HFIR. Isotopes with short half-lives are not useful for long-range environmental monitoring. However, these measurements could potentially be combined with atmospheric modeling to predict the background source term of the longer-lived Xe ratios at a monitoring station.

[Impact of the healthcare pathway on the rate of obstetrical interventions in small for gestational age fetuses (IATROPAG Study)]. / Impact du parcours de soins sur le taux d'interventions obstétricales dans la prise en charge des fœtus petit pour l'âge gestationnel (Étude IATROPAG).

BACKGROUND: While previous studies have demonstrated an improvement in implementation of clinical practices and an improved neonatal prognosis when growth restricted fetuses were followed within a standardized healthcare pathway, the objective of this study was to assess the prevalence of obstetric interventions in small-for-gestational-age (SGA) fetuses followed within a standardized care pathway compared to a traditional care pathway. METHODS: We conducted a retrospective study between 2015 and 2017, in a type III maternity hospital in Lyon, in a population of SGA fetuses, considered as such in case of antenatal diagnosis of fetal weight<10th percentile but>3rd centile without umbilical Doppler abnormality during antenatal surveillance and without ultrasound argument suggesting intrauterine growth retardation (IUGR). We collected the gestational age at diagnosis, obstetrical events and prevention of preterm delivery (antenatal corticosteroids), gestation age at birth, the method of delivery (spontaneous or induced), indication of induction, the method of birth (spontaneous, instrumental extraction or caesarean section), and the immediate neonatal outcome including cord pH, Apgar score at 5minutes, birth weight and fetal sex. After diagnosis, the choice of the pathway was left to the practitioner depending on their habit, their ability to manage the follow-up and their organizational constraints. RESULTS: Over the study period, and after exclusion of IUGR, 96 SGA were followed up in the traditional pathway and 106 SGA were followed up in the standardized pathway P=0.75. The traditional pathway showed in multivariate analysis a higher prevalence of antenatal corticosteroid therapy for SGA (16,6%) between 2015 and 2017 with OR 7.3 95% CI [1.41-38.43] when compared to the standardized pathway (3,7%). Similarly, the traditional pathway proposes a higher prevalence of induction of labor (54,1%) than the standardized pathway (33,9%) between 2015 and 2017 with OR 3.19 95% CI [1.70-7.80]. The "a posteriori" post-hoc power of the study is 82.9%. CONCLUSION: This study confirms the absence of excessive obstetrical intervention in the SGA population when followed in a standardized healthcare pathway. The latter would reduce unnecessary obstetrical interventions while respecting the intrinsic neonatal prognosis of small for gestational age fetuses.

Untargeted LC-Q-TOF mass spectrometry method for the detection of adulterations in skimmed-milk powder.

A nontargeted protein identification method was developed to screen for adulterations in skimmed-milk powder (SMP). There are indications of falsified SMP content due to the addition of plant proteins. To demonstrate the reliability and accuracy of the developed comparative LC-MS method using a quadrupole TOF MS instrument, adulterated SMP samples were prepared by the addition of protein isolates of soy and pea to skimmed-milk before pasteurisation and evaporation. The comparative LC-MS approach enabled unequivocal discrimination of those SMP samples containing soy and pea protein from nonadulterated SMP. To identify the source of (plant) proteins present in the adulterated SMP, data-dependent LC-MS/MS was used in combination with an include list of differential peptides. Numerous peptides originating from the major seed proteins of soy (glycinin, beta-conglycin) and pea (legumin, vicilin) could be identified in this way.

A density functional for sparse matter.

Sparse matter is abundant and has both strong local bonds and weak nonbonding forces, in particular nonlocal van der Waals (vdW) forces between atoms separated by empty space. It encompasses a broad spectrum of systems, like soft matter, adsorption systems and biostructures. Density-functional theory (DFT), long since proven successful for dense matter, seems now to have come to a point, where useful extensions to sparse matter are available. In particular, a functional form, vdW-DF (Dion et al 2004 Phys. Rev. Lett. 92 246401; Thonhauser et al 2007 Phys. Rev. B 76 125112), has been proposed for the nonlocal correlations between electrons and applied to various relevant molecules and materials, including to those layered systems like graphite, boron nitride and molybdenum sulfide, to dimers of benzene, polycyclic aromatic hydrocarbons (PAHs), doped benzene, cytosine and DNA base pairs, to nonbonding forces in molecules, to adsorbed molecules, like benzene, naphthalene, phenol and adenine on graphite, alumina and metals, to polymer and carbon nanotube (CNT) crystals, and hydrogen storage in graphite and metal-organic frameworks (MOFs), and to the structure of DNA and of DNA with intercalators. Comparison with results from wavefunction calculations for the smaller systems and with experimental data for the extended ones show the vdW-DF path to be promising. This could have great ramifications.

Surgical Treatment of a Medial Clavicle Fracture Nonunion with Medial Clavicle Resection and Stabilization to the Sternum with Palmaris Longus Graft.

Medial end clavicular fractures are a rare occurrence. While most of these fractures can be appropriately managed with a nonoperative treatment, some cases of symptomatic nonunion might be surgically addressed to preserve sternoclavicular joint stability and ensure favorable outcomes. The open reduction and osteosynthesis procedure is a commonly performed procedure to treat clavicular fracture nonunion. However, few revision procedures have been described to address the occasional cases of hardware failure or recurrent nonunion of the medial end. In this report, the authors present a case of symptomatic nonunion of the medial clavicle initially treated with osteosynthesis. Implant failure with hardware migration was then treated by medial clavicle resection and stabilization to the sternum using a palmaris longus autograft and the figure-of-eight lacing technique. Excellent functional outcomes at three years of follow-up were obtained. To the authors' knowledge, this is the first case reporting on a sternoclavicular stabilization with a tendon autograft for such an important bone deficit.

[Antibiotic prophylaxis in preterm premature rupture of membranes: CNGOF preterm premature rupture of membranes guidelines]. / Choix et durée de l'antibioprophylaxie en cas de rupture prématurée des membranes avant terme. RPC rupture prématurée des membranes avant terme CNGOF.

OBJECTIVE: To analyse benefits and risks of antibiotic prophylaxis in the management of preterm premature rupture of membranes. METHODS: PubMed and Cochrane Central databases search. RESULTS: Streptoccoccus agalactiae (group B streptococcus) and Escherichia coli are the two main bacteria identified in early neonatal sepsis (EL3). Antibiotic prophylaxis at admission is associated with significant prolongation of pregnancy (EL2), reduction in neonatal morbidity (EL1) without impact on neonatal mortality (EL2). Co-amoxiclav could be associated with an increased risk for neonatal necrotising enterocolitis (EL2). Antibiotic prophylaxis at admission in women with preterm premature rupture of the membranes is recommended (Grade A). Monotherapy with amoxicillin, third generation cephalosporin and erythromycin can be used as well as combination of erythromycin and amoxicillin (Professional consensus) for 7 days (GradeC). Shorter treatment is possible when initial vaginal culture is negative (Professional consensus). Co-amxiclav, aminoglycosides, glycopeptides, first and second generation cephalosporin, clindamycin and metronidazole are not recommended (Professional consensus). CONCLUSIONS: Antibiotic prophylaxis against Streptoccoccus agalactiae (group B streptococcus) and E. coli is recommended in women with preterm premature of the membranes (Grade A). Monotherapy with amoxicillin, third generation cephalosporin or erythromycin, as well as combination of erythromycin and amoxicillin are recommended (Professional consensus).

[Preterm premature rupture of membranes: CNGOF Guidelines for clinical practice - Short version]. / Rupture prématurée des membranes avant terme : recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVE: To determine management of women with preterm premature rupture of membranes (PPROM). METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus). CONCLUSION: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A).

Isolation and characterization of genes from the marine microalga Pavlova salina encoding three front-end desaturases involved in docosahexaenoic acid biosynthesis.

The marine microalga Pavlova salina produces lipids containing approximately 50% omega-3 long chain polyunsaturated fatty acids (LC-PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Three cDNA sequences, designated PsD4Des, PsD5Des, PsD8Des, were isolated from P. salina and shown to encode three front-end desaturases with Delta4, Delta5 and Delta8 specificity, respectively. Southern analysis indicated that the P. salina genome contained single copies of all three front-end fatty acid desaturase genes. When grown at three different temperatures, analysis of fatty acid profiles indicated P. salina desaturation conversions occurred with greater than 95% efficiency. Real-Time PCR revealed that expression of PsD8Des was higher than for the other two genes under normal growth conditions, while PsD5Des had the lowest expression level. The deduced amino acid sequences from all three genes contained three conserved histidine boxes and a cytochrome b(5) domain. Sequence alignment showed that the three genes were homologous to corresponding desaturases from other microalgae and fungi. The predicted activities of these three front-end desaturases leading to the synthesis of LC-PUFA were also confirmed in yeast and in higher plants.

Identification of plant proteins in adulterated skimmed milk powder by high-performance liquid chromatography -- mass spectrometry.

The EU subsidises the use of skimmed-milk powder (SMP) in compound feeding stuffs. There are indications of falsified SMP content due to the addition of plant proteins. These proteins are not allowed in SMP and cannot be identified by the official reference method. Since soy and pea proteins are most likely to be added to SMP, manufactured SMP containing 1 and 5% of these plant proteins was used to develop a sensitive protein identification method based on mass spectrometry (MS). The method included a pre-fractionation step to enrich for plant proteins by using a borate buffer. A very fast perfusion liquid chromatography method including sensitive and selective intrinsic fluorescence detection was developed for monitoring and quantifying the efficiency of the pre-fractionation and screening for plant proteins. After tryptic digestion of the enriched fraction from manufactured adulterated SMP, numerous peptides originating from the major seed proteins of soy (glycinin, beta-conglycin) and pea (legumin, vicilin) could be identified by MS/MS analysis on a quadrupole time-of-flight MS instrument.

Aspirin for Prevention of Preeclampsia.

Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are, however, the subject of much controversy. Since the first evidence of the obstetric efficacy of aspirin in 1985, numerous studies have tried to determine the effect of low-dose aspirin on the incidence of preeclampsia, with very controversial results. Large meta-analyses including individual patient data have demonstrated that aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia. However, guidelines regarding the usage of aspirin to prevent preeclampsia differ considerably from one country to another. Screening modalities, target population, and aspirin dosage are still a matter of debate. In this review, we report the pharmacodynamics of aspirin, its main effects according to dosage and gestational age, and the evidence-based indications for primary and secondary prevention of preeclampsia.

Alpha spectrometry applications with mass separated samples.

(241)Am has been deposited using a novel technique that employs a commercial inductively coupled plasma mass spectrometer. This work presents results of high-resolution alpha spectrometry on the (241)Am samples using a small area passivated implanted planar silicon detector. We have also investigated the mass-based separation capability by developing a (238)Pu sample, present as a minor constituent in a (244)Pu standard, and performed subsequent radiometric counting. With this new sample development method, the (241)Am samples achieved the intrinsic energy resolution of the detector used for these measurements. There was no detectable trace of any other isotopes contained in the (238)Pu implant demonstrating the mass-based separation (or enhancement) attainable with this technique.

In closely monitored patients, adherence in the first month predicts completion of therapy for latent tuberculosis infection.

BACKGROUND: Current therapy for latent TB infection (LTBI) is long, and requires close follow-up. This results in sub-optimal adherence-the major reason for failure of therapy. METHODS: In an open label randomised trial comparing 4 months of rifampicin with 9 months of isoniazid, the proportion and regularity of doses taken, measured with an electronic monitoring system (MEMS), and provider estimates of adherence in the first month of therapy, were assessed as predictors of treatment completion. RESULTS: Of 104 patients analysed, 86 took more than 80% of doses within the expected interval, 11 took more than 80% of doses but over a longer time interval than usually allowed, and seven did not complete treatment. Treatment completion was associated with the number of doses taken, and the variability of intervals between doses during the first month of treatment. CONCLUSIONS: Adherence in the first month, based on the number of doses and variability of times when taken, could be useful to predict completion of LTBI therapy. Interventions could be targeted to patients with suboptimal adherence in the first month.

High-performance anion-exchange chromatography combined with intrinsic fluorescence detection to determine erythropoietin in pharmaceutical products.

A high-performance anion-exchange chromatography (HPAEC) method was developed for determination of recombinant human erythropoietin (EPO) in pharmaceutical products. A fluorescence detector was added to the HPLC system as intrinsic fluorescence detection compared favourably to UV detection regarding sensitivity and selectivity. The HPLC method has been successfully applied to analyse erythropoietin products even in the presence of albumin as excipient. The intrinsic fluorescence chromatograms of both proteins revealed various peaks attributed to either micro-heterogeneous erythropoietin or albumin variants. The intrinsic fluorescence signal was linear over the range 10-200 microg/ml erythropoietin corresponding to pharmaceutically relevant concentrations. The HPLC method appeared to be a suitable method for differentation between recombinant human erythropoietin epoetin-alpha and -beta as they revealed different intrinsic fluorescence elution profiles. In conclusion, this study contributes to the development of a straightforward physicochemical method for specific quantification of recombinant human erythropoietin in pharmaceutical preparations.

HPLC and tandem detection to monitor conformational properties of biopharmaceuticals.

High-performance liquid chromatography (HPLC) with UV, circular dichroism (CD) and intrinsic fluorescence detection was applied to monitor conformational properties of recombinant human interferon alpha2b when performing size exclusion chromatography (SEC) and reversed-phase HPLC (RP-HPLC). In this way native conditions during SEC and structural changes of the protein during RP-HPLC were demonstrated. These results were confirmed by stand-alone fluorescence and CD measurements. With respect to HPLC tandem detection, the fluorescence detector compared favourably to the UV and CD detector regarding linearity, sensitivity and selectivity. SEC combined with intrinsic fluorescence scanning detection permits conformational analysis of small amounts of aggregates in the presence of excess native monomeric protein. In conclusion, HPLC with on-line UV and intrinsic fluorescence detection provides a promising concept for analysing the amount and conformational properties of a biopharmaceutical and its impurities.

Big Data and the Global Public Health Intelligence Network (GPHIN).

BACKGROUND: Globalization and the potential for rapid spread of emerging infectious diseases have heightened the need for ongoing surveillance and early detection. The Global Public Health Intelligence Network (GPHIN) was established to increase situational awareness and capacity for the early detection of emerging public health events. OBJECTIVE: To describe how the GPHIN has used Big Data as an effective early detection technique for infectious disease outbreaks worldwide and to identify potential future directions for the GPHIN. FINDINGS: Every day the GPHIN analyzes over more than 20,000 online news reports (over 30,000 sources) in nine languages worldwide. A web-based program aggregates data based on an algorithm that provides potential signals of emerging public health events which are then reviewed by a multilingual, multidisciplinary team. An alert is sent out if a potential risk is identified. This process proved useful during the Severe Acute Respiratory Syndrome (SARS) outbreak and was adopted shortly after by a number of countries to meet new International Health Regulations that require each country to have the capacity for early detection and reporting. The GPHIN identified the early SARS outbreak in China, was credited with the first alert on MERS-CoV and has played a significant role in the monitoring of the Ebola outbreak in West Africa. Future developments are being considered to advance the GPHIN's capacity in light of other Big Data sources such as social media and its analytical capacity in terms of algorithm development. CONCLUSION: The GPHIN's early adoption of Big Data has increased global capacity to detect international infectious disease outbreaks and other public health events. Integration of additional Big Data sources and advances in analytical capacity could further strengthen the GPHIN's capability for timely detection and early warning.