Specialist Networks Influence Clinician Willingness to Treat Individuals with Special Needs.

BACKGROUND: The South Australian Dental Service's Special Needs Network was established to support oral health professionals working within their statewide government-funded dental service to treat patients with special needs. This study aimed to investigate how a structured network relationship with specialists in special needs dentistry influenced the willingness of dentists to treat this group of patients. METHODS: Semi-structured interviews were used to explore the views of specialists and dentists involved in the South Australian Dental Service's Special Needs Network. Inductive thematic analysis identified emerging themes enabling completion of a SWOT (strengths, weaknesses, opportunities, threats) analysis. RESULTS: Dentists felt that a strength of the Network was a greater sense of collegiality, particularly for those working in rural areas. Although the inability to get immediate advice was seen as a weakness, dentists felt a more structured relationship with specialists improved communication pathways and resulted in more timely care. The aging workforce, systemic barriers in the public dental system, such as productivity pressures and infrastructure, and the lack of support from other health professionals were seen as ongoing barriers and threats. Regardless, dentists identified the use of telehealth and visiting specialists as future opportunities. Specialists felt that the Network was a valuable resource but were skeptical about its effectiveness, feeling that a limitation was the ability of dentists to recognize the complexity of cases. CONCLUSIONS: Ongoing support from and communication with specialists in special needs dentistry through a structured network improved the perceived ability and willingness of dentists to treat patients with special needs. KNOWLEDGE TRANSFER STATEMENT: This research suggests that providing support to dentists through a hub-and-spoke network that facilitates additional training, professional interaction, and improved communication with specialists in special needs dentistry may help overcome some of the current barriers to access to care experienced by individuals with special needs, particularly those associated with the willingness and capability of clinicians treat them.

The association between serum prealbumin and poor outcome in COVID-19 - Systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the association between the prealbumin and severity and mortality in COVID-19. MATERIALS AND METHODS: We performed a systematic literature search from PubMed, Embase, and Scopus databases up until 2 February 2021. The primary outcome was the poor outcome, a composite of mortality and severity. Severe COVID-19 was defined as COVID-19 that fulfill the criteria for severe pneumonia or patients with acute respiratory distress syndrome/disease progression/need for intensive care unit or mechanical ventilation. The effect estimates were a mean difference between patients with and without a poor outcome in mg/dL and odds ratio (OR) per 1 mg/dL decrease in prealbumin level. The effect estimates were reported with their 95% confidence interval (95% CI). RESULTS: Nine studies comprising of 2104 patients were included in this systematic review and meta-analysis. Patients with poor outcome have lower prealbumin level (mean difference -71.48 mg/dL [95% CI -93.74, -49.22], p<0.001; I2: 85.9%). Every 1 mg/dL decrease in prealbumin level was associated with 1% increase in poor outcome (OR 0.992 [0.987, 0.997], p=0.004, I2: 81.7%). Meta-regression analysis showed that the association between the prealbumin level and poor outcome varies with gender (male) (coefficient: 3.50, R2: 100%, p<0.001), but not age, diabetes, hypertension, and chronic kidney disease. CONCLUSIONS: Low serum prealbumin was associated with poor outcomes in patients with COVID-19.

Body mass index and outcome in patients with COVID-19: A dose-response meta-analysis.

BACKGROUND: There is mounting evidence related to the association between obesity and severity of COVID-19. However, the direct relationship of the increase in the severe COVID-19 risk factors, with an increase in body mass index (BMI), has not yet been evaluated. AIM: This meta-analysis aims to evaluate the dose-response relationship between body mass index (BMI) and poor outcome in patients with COVID-19. METHODS: A systematic literature search was conducted using PubMed, Europe PMC, ProQuest, and the Cochrane Central Database. The primary outcome was composite poor outcome composed of mortality and severity. The secondary outcomes were mortality and severity. RESULTS: A total of 34,390 patients from 12 studies were included in this meta-analysis. The meta-analysis demonstrated that obesity was associated with composite poor outcome (OR 1.73 [1.40, 2.14], P<0.001; I2: 55.6%), mortality (OR 1.55 [1.16, 2.06], P=0.003; I2: 74.4%), and severity (OR 1.90 [1.45, 2.48], P<0.001; I2: 5.2%) in patients with COVID-19. A pooled analysis of highest BMI versus reference BMI indicate that a higher BMI in the patients was associated with composite poor outcome (aOR 3.02 [1.82, 5.00], P<0.001; I2: 59.8%), mortality (aOR 2.85 [1.17, 6.92], P=0.002; I2: 79.7%), and severity (aOR 3.08 [1.78, 5.33], P<0.001; I2: 11.7%). The dose-response meta-analysis showed an increased risk of composite poor outcome by aOR of 1.052 [1.028, 1.077], P<0.001 for every 5kg/m2 increase in BMI (Pnon-linearity<0.001). The curve became steeper with increasing BMI. CONCLUSION: Dose-response meta-analysis demonstrated that increased BMI was associated with increased poor outcome in patients with COVID-19.

Effect of chronic obstructive pulmonary disease and smoking on the outcome of COVID-19.

OBJECTIVE: To investigate the association between chronic obstructive pulmonary disease (COPD) and smoking with outcome in patients with COVID-19.METHODS: A systematic literature search was performed using PubMed, EuropePMC, SCOPUS and the Cochrane Central Database. A composite of poor outcome, mortality, severe COVID-19, the need for treatment in an intensive care unit (ICU) and disease progression were the outcomes of interest.RESULTS: Data on 4603 patients were pooled from 21 studies. COPD was associated with an increased risk for composite poor outcome (OR 5.01, 95%CI 3.06-8.22; P < 0.001; I² 0%), mortality (OR 4.36, 95%CI 1.45-13.10; P = 0.009; I² 0%), severe COVID-19 (OR 4.62, 95%CI 2.49-8.56; P < 0.001; I² 0%), ICU care (OR 8.33, 95%CI 1.27-54.56; P = 0.03; I² 0%), and disease progression (OR 8.42, 95%CI 1.60-44.27; P = 0.01; I² 0%). Smoking was found to increase the risk of composite poor outcome (OR 1.52, 95%CI 1.16-2.00; P = 0.005; I² 12%), and subgroup analysis showed that smoking was significant for increased risk of severe COVID-19 (OR 1.65, 95%CI 1.17-2.34; P = 0.004; I² 11%). Current smokers were at higher risk of composite poor outcomes (OR 1.58, 95%CI 1.10-2.27; P = 0.01; I² 0%) than former/non-smokers.CONCLUSION: Our systematic review and meta-analysis revealed that COPD and smoking were associated with poor outcomes in patients with COVID-19.

Plant-based chimeric HPV-virus-like particles bearing amyloid-ß epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer's disease brains.

The main amyloid-beta (Aß) variants detected in the human brain are full-length Aß1-40 and Aß1-42 peptides; however, a significant proportion of AD brain Aß consists also of N-terminal truncated/modified species. The majority of the previous immunotherapeutic strategies targeted the N-terminal immunodominant epitope of the full-length Aß; however, most of the pathological N-truncated forms of Aß lack this critical B cell epitope. Recently, virus-like particles (VLPs), self-assembled structures with highly ordered repetitive patterns on their surface and capable of inducing robust immune responses, were applied as a promising platform for various antigen expressions. In this study, we expressed in plants two chimeric HPV16 L1 capsid proteins obtained by introduction of the ß-amyloid 11-28 epitope (Aß 11-28) into the h4 helix or into the coil regions of the L1 protein. The Aß 11-28 epitope was chosen because it is present in the full-length Aß 1-42 as well as in the truncated/modified amyloid peptide species. After expression, we assembled the chimerical L1/Aß 11-28 into a VLP in which the Aß 11-28 epitope is exposed at very high density (360 times) on the surface of the VLP. The chimeric VLPs elicited in mice Aß-specific antibodies binding to ß-amyloid plaques in APP-tg mouse and AD brains. Our study is the first to demonstrate a successful production in plants and immunogenic properties in mice of chimeric HPV16 L1 VLPs bearing Aß epitope that may be of potential relevance for the development of multivalent vaccines for a multifactorial disease such as AD.

Kidney Transplantation From a Donor With Sickle Cell Disease.

In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.

Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease.

A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease.

The complete genome sequence and genome structure of frangipani mosaic virus.

In this study, the complete sequence of the genomic RNA of frangipani mosaic virus (FrMV) has been determined and compared to those of other known tobamoviruses. The complete genome sequence of FrMV consisted of 6,643 nucleotides. The FrMV genomic RNA encoded four open reading frames (ORFs), for proteins of M(r) 128 kDa (1,147 aa), 186 kDa (1,651 aa), 30 kDa (257 aa) and 18 kDa (175 aa) from the 5' to the 3' end. Overall similarities for the four ORFs of FrMV-P ranged from 26.8 to 53.0% at the amino acid level when compared to those of 24 other tobamoviruses. Phylogenetic analysis of the FrMV replicase (186 kDa) and MP revealed that FrMV is closely related to SHMV and CMMoV, while the FrMV replicase (128 kDa) is more closely related to cucurbit-infecting and malvaceous-infecting tobamoviruses, and the FrMV CP is closely related to that of CMMoV and solanaceous-infecting tobamoviruses.

Development of an edible rabies vaccine in maize using the Vnukovo strain.

The objective of this study was to obtain transgenic maize expressing the rabies virus glycoprotein (G) of the Vnukovo strain and to evaluate its immunogenicity in mice, by the oral route. The ubiquitin maize promoter fused to the whole coding region of the rabies virus G gene, and a constitutive promoter from cauliflowermosaic virus (CaMV)were used. Maize embryogenic callus were transformed with the above construct by biolistics. Regenerated maize plants were recovered and grown in a greenhouse. The presence of the G gene and its product was detected by PCR and western blot, respectively. The amount of G protein detected in the grains was approximately 1% of the total soluble plant protein. Transformed kernels containing 50 microg of G protein were given once by the oral route in adult mice (BALB-C strain). Challenge was undertaken at 90-days post-vaccination using a lethal dose of a vampire bat rabies virus (100 LD 50% in mice); vampire bats are one of the main reservoirs in Latin America. The edible vaccine induced viral neutralizing antibodies (VNA) which, protected mice 100% against challenge. The control group did not survive. The G protein of the Vnukovo strain expressed in transgenic maize may be considered as an oral immunogen against rabies, conferring cross-protection.

Clonidine, octopaminergic receptor agonist, reduces protein feeding in the blow fly, Phormia regina (Meigen).

Results in this study are consistent with those of Murdock and his colleagues who clearly demonstrated that clonidine, an agonist of octopaminergic receptors in some insects, significantly increases sucrose feeding. Their studies, however, did not examine the effect of clonidine on protein feeding. Injection of a 20 microg/microl/fly dose of clonidine significantly reduces protein feeding in both sexes of Phormia regina, instead of stimulating feeding as is observed with carbohydrate feeding. The manner in which the flies are fed prior to starvation and the method of testing influences the amounts of diet consumed. It is proposed that the biogenic amines influence the state of hunger (i.e., protein versus carbohydrates) while other chemicals and neural mechanisms (i.e., such as sulfakinins and stretch receptors, respectively) affect satiety.

Blood concentrations of amitriptyline and its metabolite in rats after acute oral administration of amitriptyline.

Amitriptyline (AMT), a tricyclic antidepressant that is a dibenzocycloheptadine derivative, is frequently used. However, the case reports of AMT-related fatalities are increased, nowadays, due to the low levels of toxic and fatal concentration in blood. So, this study was carried out to determine the concentrations of AMT and its demethylated metabolite, nortriptyline (NTR), after acute single oral administration of AMT in rats. Blood samples were collected five times from the ophthalmic venous plexus at 0, 1, 2, 4, and 8 h after acute single oral administration of AMT in toxic doses of 10 (Group I) or 20 mg/kg (Group II), and the concentrations of AMT and NTR and the mean ratios of AMT to NTR (AMT/NTR) in the blood were periodically determined at designated times. The blood concentrations of AMT and NTR were identified and quantitated by gas chromatography with thermionic specific detection and gas chromatography-mass spectrometry after solid-phase extraction with a Clean Screen DAU column. The peak blood concentrations of AMT and NTR in Group I were 0.34 and 0.28 microg/mL, respectively, and those of AMT and NTR in Group II were 0.59 and 0.43 microg/mL, respectively, and were reached at 1 h after single oral administration.

The use of cysteine proteinase inhibitors to engineer resistance against potyviruses in transgenic tobacco plants.

As the processing mechanism of all known potyviruses involves the activity of cysteine proteinases, we asked whether constitutive expression of a rice cysteine proteinase inhibitor gene could induce resistance against two important potyviruses, tobacco etch virus (TEV) and potato virus Y (PVY), in transgenic tobacco plants. Tobacco lines expressing the foreign gene at varying levels were examined for resistance against TEV and PVY infection. There was a clear, direct correlation between the level of oryzacystatin message, inhibition of papain (a cysteine proteinase), and resistance to TEV and PVY in all lines tested. The inhibitor was ineffective against tobacco mosaic virus (TMV) infection because processing of this virus does not involve cysteine proteinases. These results show that plant cystatins can be used against different potyviruses and potentially also against other viruses, whose replication involves cysteine proteinase activity.

Perspective: edible vaccines--a concept coming of age.

In addition to their traditional role as a source of natural medicines, it is now possible to genetically engineer plants to produce pharmaceuticals. Transgenic plants expressing antigens from pathogenic microorganisms offer many advantages as low-cost production systems and effective delivery systems for vaccines. This new technology might contribute to global vaccine programs and might have a dramatic impact on health care in developing countries.

Peroxisomal thiolase mRNA is induced during mango fruit ripening.

Fruit ripening is a complex, developmentally regulated process. A series of genes have been isolated from various ripening fruits encoding enzymes mainly involved in ethylene and cell wall metabolism. In order to aid our understanding of the molecular basis of this process in a tropical fruit, a cDNA library was prepared from ripe mango (Mangifera indica L. cv. Manila). By differential screening with RNA poly(A)+ from unripe and ripe mesocarp a number of cDNAs expressing only in ripe fruit have been isolated. This paper reports the characterization of one such cDNA (pTHMF 1) from M. indica which codes for a protein highly homologous to cucumber, rat and human peroxisomal thiolase (EC 2.3.1.16), the catalyst for the last step in the beta-oxidation pathway. The cDNA for the peroxisomal mango thiolase is 1305 bp in length and codes for a protein of 432 amino acids with a predicted molecular mass of 45,532 Da. Mango thiolase is highly homologous to cucumber thiolase (80%), the only other plant thiolase whose cloning has been reported, and to rat and human thiolases (55% and 55% respectively). It is shown by northern analysis that during fruit ripening THMF 1 is up-regulated. A similar pattern of expression was detected in tomato fruit. Wounding and pathogen infection do not appear to affect THMF 1 expression. The possible involvement of thiolase in fatty acid metabolism during fruit ripening will be discussed. To our knowledge this is the first report cloning of a plant gene involved in fatty acid metabolism showing an induction during fruit ripening.

Alternative oxidase from mango (Mangifera indica, L.) is differentially regulated during fruit ripening.

Alternative oxidase is a respiratory-chain component of higher plants and fungi that catalyzes cyanide-resistant oxygen consumption. The activity of a alternative oxidase has been detected during ripening in several climacteric fruit including mango (Mangifera indica L.). Synthetic oligonucleotides, corresponding to conserved regions of the Sauromatum guttatum and Arabidopsis thaliana nucleotide sequences, were used as primers for polymerase chain reaction to amplify genomic DNA extracted from mango leaves. The 623-bp fragment was found to encode an open reading frame of 207 amino acids showing high identity to the S. guttatum enzyme. Using this fragment to screen a ripe mango mesocarp cDNA library, one full-length cDNA clone, designated pAOMI.1, was obtained that contained an open reading frame encoding a polypeptide of 318 amino acids. The predicted amino-acid sequence exhibited 62, 64 and 68% identity to the S. guttatum, soybean, and A. thaliana enzymes respectively, indicating that this cDNA encodes a mango homologue of the alternative oxidase. Gel blot hybridization showed that pAOMI.1 is likely to be encoded by a single-copy gene. The 1.6 kb-transcript was induced during mango fruit ripening although the transcript was clearly detectable in unripe and developing fruit. Antibodies raised against the S. guttatum enzyme recognized three bands of approximately 27, approximately 33 and approximately 36 kDa from mitochondrial mango proteins. Two of the bands were detectable before ripening and increase in ripe fruit, the other band (27 kDa) was barely present in unripe fruit but accumulated during ripening. The clone pAOMI.1 was able to complement an Escherichia coli hemA mutant deficient in cytochrome-mediated aerobic respiration. This is the first report on the analysis of alternative oxidase at the molecular level during the ripening of a climacteric fruit.

Isolation and characterization of a gene involved in ethylene biosynthesis from Arabidopsis thaliana.

The ethylene forming enzyme (EFE) is a key factor in ethylene biosynthesis. To understand better the regulation of ethylene biosynthesis in vegetative tissues, we set out to isolate and characterize a complementary DNA (cDNA) encoding the EFE from Arabidopsis thaliana. An A. thaliana cDNA library was screened with pTOM 13, a tomato cDNA coding for the EFE. A cDNA clone (pEAT1) was isolated. The cDNA is 1200 nucleotides (nt) in length and predicts a protein of M(r) 36,663. The insert includes the complete open reading frame of 972 bp and shows strong homology with several reported sequences, both at the nt and amino acid level. In whole seedlings, expression of pEAT1 was enhanced by wounding, ethrel, Fe2+, and 1-amino-cyclopropane-carboxylic acid (ACC) treatments. In contrast, heat shock had no effect on the expression.

Double-blind trial to find dose range using a fixed combination of mefloquine, sulfadoxine and pyrimethamine in falciparum malaria: a field study on adults in Burma.

In a field study conducted in Burma, 60 semi-immune adults were randomly assigned to 2 treatment groups. The first (mean parasite count, 12717/mm3) received a single dose of a fixed combination of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets of 'Fansimef') plus 1 tablet placebo. The second group (mean parasite count, 11 863/mm3) were given 3 tablets of the same medication. The study was double-blind. Parasite count was checked daily for the first week and weekly for a further 3 weeks. Average times for parasite clearance were 1.47 d in patients receiving 2 tablets, and 1.87 d in those given 3 tablets. Asexual parasites reappeared on day 28 in one patient in each group, although they had been free of parasites during the previous 4 weeks; this could be due to reinfection. The drugs were generally well tolerated, though mild and transient giddiness was seen in 80% of patients in the first group and 96% in the second. Nausea was reported by 33% and 43% of patients respectively. No vomiting occurred in the first group but 8 patients vomited in the second (P less than 0.01). In conclusion it seems possible to treat falciparum malaria in semi-immune adults, weighing less than 60 kg, with a single dose of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets), instead of the higher dose (3 tablets) currently recommended. This reduces treatment cost and improves tolerance of the drugs.

Characteristics of normal labour among different racial groups in Malaysia.

The characteristics of normal labour in 977 Malay, Chinese and Indian parturients were established from a retrospective study. Indian babies were found to be significantly smaller than Malay babies which were significantly smaller than Chinese babies (P less than 0-05, P less than 0-05). The mean duration of the first stage of labour taken from the time of admission to the labour ward was 3-4 hours in primiparae and 2-7 hours in multiparae. The mean durations of the second stage of labour were 23-7 minutes and 13-1 minutes respectively. Curves of mean dilatation of cervix and probit analysis at 80% revealed significant differences in the progress of normal labour in primiparae among the three racial groups. The Indian primiparae not only had a slower rate of cervical dilatation but seemed to reach the accelerated phase of dilatation later. No significant differences were noticed in the labours of multiparae.