A nationwide population-based cohort study of the incidence of severe and rare infections among adults with psoriasis in Denmark.

BACKGROUND: Patients with psoriasis have a high risk for multiple comorbid conditions. However, few studies have examined the association between psoriasis and severe and rare infections. This study reports the incidence of severe and rare infections (considered as rare in Denmark) among Danish patients with psoriasis, compared with the general population. OBJECTIVES: The objectives of this study were to assess the incidence and risk of severe and rare infections in Danish patients with psoriasis and the matched general population, and to compare this risk for patients with severe or mild psoriasis with that of the general population. METHODS: Data for individuals aged ≥18 years who were alive and resident in the source population were collected from the Danish National Patient Register between 1 January 1997 and 31 December 2018. Individuals with any of the investigated chronic infections prior to inclusion were excluded. Patients with psoriasis were matched (1 : 6) for age and sex with general population controls. Severe infections were defined as infections requiring treatment in a hospital setting and rare infections included HIV, hepatitis B and C, and tuberculosis infections. Incidence rates (IRs) were reported per 100 000 person-years of exposure. Severe psoriasis was defined according to previous or active use of systemic or biological treatment. Patients who never received biological and/or systemic treatment were categorized as having mild psoriasis. RESULTS: A total of 94 450 patients with psoriasis were matched with 566 700 controls. The respective IRs were higher for patients with any psoriasis compared with controls; IR 3104·9 [95% confidence interval (CI) 3066·6 to 3143·7] and IR 2381·1 (95% CI 2367·6 to 2394·6) for any infection, IR 3080·6 (95% CI 3042·5 to 3119·3) and IR 2364·4 (95% CI 2350·9 to 2377·9) for severe infections, and IR 42·9 (95% CI 38·89 to 47·4) and IR 31·8 (95% CI 30·34 to 33·3) for rare infections, respectively. Patients with severe psoriasis had higher IRs of severe or rare infections (IR 3847·7, 95% CI 3754·3 to 3943·4) compared with patients with mild psoriasis and controls. CONCLUSIONS: As the severity of psoriasis increases, so does the risk of severe and rare infections. Therefore, clinicians should be aware of the increased risk of severe and rare infections in patients with severe psoriasis so that early investigation and treatment can be initiated. What is already known about this topic? Few studies have looked at the incidence and prevalence of serious infections (associated with hospitalization) and rare infections including tuberculosis, hepatitis B and C, and HIV among patients with different severities of psoriasis. What does this study add? Patients with psoriasis have an increased risk of severe and rare infections. Clinicians should be aware of the increased risk of severe and rare infections in patients with severe psoriasis so that early investigation and treatment can be initiated.

Long-term Safety of Secukinumab Over Five Years in Patients with Moderate-to-severe Plaque Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis: Update on Integrated Pooled Clinical Trial and Post-marketing Surveillance Data.

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified.

Dissolution Improvement of Progesterone and Testosterone via Impregnation on Mesoporous Silica Using Supercritical Carbon Dioxide.

Progesterone (PRG) and testosterone (TST) were impregnated on mesoporous silica (ExP) particles via supercritical carbon dioxide (scCO2) processing at various pressures (10-18 MPa), temperatures (308.2-328.2 K), and time (30-360 min). The impact of a co-solvent on the impregnation was also studied at the best determined pressure and temperature. The properties of the drug embedded in silica particles were analysed via gas chromatography (GC), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and nitrogen adsorption. An impregnation of 1 to 82 mg/g for PRG and 0.1 to 16 mg/g for TST was obtained depending on the processing parameters. There was a significant effect of pressure, time, and co-solvent on the impregnation efficiency. Generally, an increase in time and pressure plus the use of co-solvent led to an improvement in drug adsorption. Conversely, a rise in temperature resulted in lower impregnation of both TST and PRG on ExP. There was a substantial increase in the dissolution rate (> 90% drug release within the first 2 min) of both TST and PRG impregnated in silica particles when compared to the unprocessed drugs. This dissolution enhancement was attributed to the amorphisation of both drugs due to their adsorption on mesoporous silica.

Mesoporous silica particles as potential carriers for protein drug delivery: protein immobilization and the effect of displacer on γ-globulin release.

The adsorption of γ-globulin was evaluated with experiments with silica particles marketed as Syloid AL1-FP (SAL), XDP-3150 (SXDP), and 244FP (SFP). The influence of pH, pore sizes, and degree of surface porosity on the extent of γ-globulin immobilization was examined. Protein adsorption on these particles was largely related to their surface porosity and pore sizes. The adsorption capacity was established to be greater with mesoporous SFP and SXDP particles at 474 and 377 mg/g, respectively, when compared to significantly low-porosity SAL (16 mg/g). Additionally, γ-globulin immobilization was favored at pH closer to iso-electric point. A key aim of this work was to better understand and improve the limited reversibility of protein adsorption. Protein desorption was found to be lower in simulated intestinal fluid (SIF) in comparison to pH 7.4 phosphate buffer (PB). The use of displacer molecules (sodium dodecyl sulfate [SDS]/Tween 80/Pluronic F127 [PF127]) promoted protein desorption from the adsorbent surface by the exchange mechanism. The PF127 provided substantial release in both studied condition but the highest release of 83% of γ-globulin from SXDP was obtained with tween 80 in PB. The released protein was analyzed with circular dichroism (CD) spectroscopy which indicated that the secondary structure of desorbed γ-globulin was dependent on the pH and displacer molecule. The conformation largely remained unchanged when desorption was carried out in SIF but changed markedly in PB specially in the presence of SDS.

Drug-Smectite Clay Amorphous Solid Dispersions Processed by Hot Melt Extrusion.

The aim of this study was to introduce smectite clay matrices as a drug delivery carrier for the development of amorphous solid dispersions (ASD). Indomethacin (IND) was processed with two different smectite clays, magnesium aluminium and lithium magnesium sodium silicates, using hot melt extrusion (HME) to prepare solid dispersions. Scanning electron microscopy (SEM), powdered X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were used to examine the physical form of the drug. Energy-dispersive X-ray (EDX) spectroscopy was used to investigate the drug distribution, and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopic analysis was done to detect any chemical interaction between these two kinds. Both PXRD and DSC analyses showed that drug-clay solid dispersion contained IND in amorphous form. EDX analysis showed a uniform IND dispersion in the extruded powders. ATR-FTIR data presented possible drug and clay interactions via hydrogen bonding. In vitro drug dissolution studies revealed a lag time of about 2 h in the acidic media and a rapid release of IND at pH 7.4. The work demonstrates that preparation of amorphous solid dispersion using inorganic smectite clay particles can effectively increase the dissolution rate of IND.

Immediate-early gene Homer1a intranuclear transcription focus intensity as a measure of relative neural activation.

Immediate-early genes (IEGs) exhibit a rapid, transient transcription response to neuronal activation. Fluorescently labeled mRNA transcripts appear as bright intranuclear transcription foci (INF), which have been used as an all-or-nothing indicator of recent neuronal activity; however, it would be useful to know whether INF fluorescence can be used effectively to assess relative activations within a neural population. We quantified the Homer1a (H1a) response of hippocampal neurons to systematically varied numbers of exposures to the same places by inducing male Long-Evans rats to run laps around a track. Previous studies reveal relatively stable firing rates across laps on a familiar track. A strong linear trend (r2 > 0.9) in INF intensity was observed between 1 and 25 laps, after which INF intensity declined as a consequence of dispersion related to the greater elapsed time. When the integrated fluorescence of the entire nucleus was considered instead, the linear relationship extended to 50 laps. However, there was only an approximate doubling of H1a detected for this 50-fold variation in total spiking. Thus, the intranuclear H1a RNA fluorescent signal does provide a relative measure of how many times a set of neurons was activated over a ~10 min period, but the dynamic range and hence signal-to-noise ratios are poor. This low dynamic range may reflect previously reported reductions in the IEG response during repeated episodes of behavior over longer time scales. It remains to be determined how well the H1a signal reflects relative firing rates within a population of neurons in response to a single, discrete behavioral event.

Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole.

This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0-1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation.

Postnatal development of Homer1a in the rat hippocampus.

Homer1a (H1a) is an immediate early gene involved in multiple forms of synaptic plasticity. It exhibits a postnatal increase in the rat forebrain (Brakeman et al. (1997) Nature 386:284-288) and reduces the density and size of dendritic spines in hippocampal neurons (Sala et al. (2003) J Neurosci 23:6327-6337). We evaluated hippocampal H1a expression at different postnatal ages (P3, P5, P7, P9, P15, P19, P23, P35, and adult) using Fluorescence In Situ Hybridization (FISH) and qRT-PCR. Maximal electroconvulsive shock (MECS) was used to induce maximal expression relative to home cage (HC) controls. Large scale images and confocal z-stacks from dorsal subiculum (DS), CA1, CA3, and dentate gyrus (DG) were analyzed by both manual and automated methods. In DS, CA1, and CA3 a significant proportion of cells (40%) expressed small but detectable levels of H1a from P3; however, MECS did not up-regulate H1a during the first postnatal week. MECS induced H1a positive cells during the second postnatal week and induction reached adult levels at P9. H1a-Intra Nuclear Foci (INF) size and intensity varied with age, increasing at P19-23 in CA1 and CA3 and from P9 to P23 in DS. In DG, H1a expression exhibited a lamination pattern and an H1a-INF size and intensity gradient across the granule cell layer, consistent with the outside-in maturation of DG granule cells. The developmental progression of H1a corresponds to the synaptic refinement period supporting the conclusion that H1a could play an important role in this process.

Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.

In recent years, there have been a growing number of small and large molecules that could be used to treat diseases of the central nervous system (CNS). Nose-to-brain delivery can be a potential option for the direct transport of molecules from the nasal cavity to different brain areas. This review aims to provide a compilation of current approaches regarding drug delivery to the CNS via the nose, with a focus on biologics. The review also includes a discussion on the key benefits of nasal delivery as a promising alternative route for drug administration and the involved pathways or mechanisms. This article reviews how the application of various auxiliary agents, such as permeation enhancers, mucolytics, in situ gelling/mucoadhesive agents, enzyme inhibitors, and polymeric and lipid-based systems, can promote the delivery of large molecules in the CNS. The article also includes a discussion on the current state of intranasal formulation development and summarizes the biologics currently in clinical trials. It was noted that significant progress has been made in this field, and these are currently being applied to successfully transport large molecules to the CNS via the nose. However, a deep mechanistic understanding of this route, along with the intimate knowledge of various excipients and their interactions with the drug and nasal physiology, is still necessary to bring us one step closer to developing effective formulations for nasal-brain drug delivery.

Melting Point Depression of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Polymers in Supercritical Carbon Dioxide in the Presence of Menthol as a Solid Co-Plasticiser.

The melting behaviour of the triblock polymers, Pluronic F38, F68, F77, F108, and F127, was investigated in pressurised CO2 and in the presence of menthol. The melting points of the polymers combined with 0, 10, 25, and 50 wt% of menthol were studied at atmospheric pressure and compared with those at 10 and 20 MPa in supercritical carbon dioxide (scCO2). The highest melting point depressions of 16.8 ± 0.5 °C and 29.0 ± 0.3 °C were observed at 10 and 20 MPa, respectively. The melting point of triblock polymers in pressurised CO2 was found to be dependent on molecular weight, poly(propylene oxide) (PPO) content, and menthol percentage. The melting point of most of the polymers studied in this work can be reduced to room temperature, which can be pivotal to the formulation development of thermolabile substances using these polymers.

COVID-19: The disease of loneliness and solitary demise.

The birth of the COVID-19 pandemic has transformed working lives of British Asian general practitioners (GPs), such as one of the authors. The effects of the national lockdown and the subsequent loneliness have impacted every aspect of our lives and increased mental health problems. The added social isolation of local lockdowns, such as in Leicester, will undoubtedly exacerbate some health problems due to a lack of patient willingness to attend healthcare services and the postponement of some appointments. The lack of culturally competent support is likely to add to the isolation in non-English-speaking people. Thus, we should pre-empt these issues in a culturally effective manner. To prepare for subsequent waves, GPs are risk-stratifying patients for COVID-19 and have commenced ReSPECT care-plan conversations with higher-risk patients. But with the increased risk from COVID-19 to Black, Asian and minority ethnic patients, should this and other groups of patients also have a ReSPECT care plan? Is now the time to consider community-hospice settings for our palliative COVID-19 patients? This pandemic has uncovered a training need for healthcare professionals to feel more comfortable in discussing end of life as an integral consultation component. We should focus our efforts in alleviating suffering by achieving 'shared understanding' and 'negotiating management' of our ReSPECT conversations.

Recovery, restoration, and risk: a cross-sectional survey of the impact of COVID-19 on GPs in the first UK city to lock down.

BACKGROUND: The COVID-19 pandemic has impacted GPs immensely. Work patterns have changed, risk stratification has been proposed, and the mental health of clinicians has been adversely affected. The COVID-19 prevalence among GPs is unknown. This study focuses on assessing the impact of COVID-19 on GPs in Leicestershire, the first UK city to lock down locally. AIM: This survey assessed the prevalence of COVID-19 in GPs and explored GP work patterns in comparison with national guidance. It used a validated perceived stress tool to evaluate the impact of COVID-19 on GP stress perception. DESIGN & SETTING: The cross-sectional retrospective survey was sent to all the GPs in Leicestershire. METHOD: A total of 111 GPs in Leicestershire took part voluntarily in an anonymised questionnaire-based study. A 29-item survey using SmartSurvey software was designed with multiple choice and Likert response scale questions. RESULTS: COVID-19 prevalence in GPs in Leicestershire was 8.1%; 70.3% of GPs were of Black, Asian, and minority ethnic (BAME) origin; 91.9% of GPs had undergone risk stratification; and 79.3% of GPs felt supported by their practice, but only 59.5% felt supported with mental health. GPs described feeling more stressed during the COVID-19 pandemic than they had been previously. CONCLUSION: This is the first study evaluating COVID-19 prevalence among GPs in Leicestershire. Despite government interventions, GPs felt less supported with their mental health compared with pre-COVID-19 times. Thus, the NHS in England should focus on GP stress and wellbeing as they work towards the restoration and recovery of primary care while battling the second wave.

Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer's glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug-polymer ratio on the successful preparation of SDs. The SIM-SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug-polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM-SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM-SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Advances in Twin-Screw Granulation Processing.

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process variables and the wide range of processed materials. Most importantly, TSG offers the benefits of both batch and continuous manufacturing for pharmaceutical products, accompanied by excellent process control, high product quality which can be achieved through the implementation of Quality by Design (QbD) approaches and the integration of Process Analytical Tools (PAT). Here, we present basic concepts of the various twin-screw granulation techniques and present in detail their advantages and disadvantages. In addition, we discuss the detail of the instrumentation used for TSG and how the critical processing paraments (CPP) affect the critical quality attributes (CQA) of the produced granules. Finally, we present recent advances in TSG continuous manufacturing including the paradigms of modelling of continuous granulation process, QbD approaches coupled with PAT monitoring for granule optimization and process understanding.

Relationships between cerebrovascular reactivity, visual-evoked functional activity, and resting-state functional connectivity in the visual cortex and basal forebrain in glaucoma.

Glaucoma is primarily considered an eye disease with widespread involvements of the brain. Yet, it remains unclear how cerebrovasculature is regulated in glaucoma and how different brain regions coordinate functionally across disease severity. To address these questions, we applied a novel whole-brain relative cerebrovascular reactivity (rCVR) mapping technique using resting-state functional magnetic resonance imaging (fMRI) without gas challenges to 38 glaucoma patients and 21 healthy subjects. The relationships between rCVR, visual-evoked fMRI response, and resting-state functional connectivity in glaucoma were then established. In the visual cortex, rCVR has a decreasing trend with glaucoma severity (p<0.05), and is coupled with visual-evoked response and functional connectivity in both hemispheres (p<0.001). Interestingly, rCVR in the basal forebrain (BF) has an increasing trend with glaucoma severity (p<0.05). The functional connectivity between right diagonal band of Broca (a sub-region of BF) and lateral visual cortex decreases with glaucoma (p<0.05), while such connectivity is inversely coupled with rCVR in the BF (p<0.05), but not the visual cortex. Overall, we demonstrate opposite trends of rCVR changes in the visual cortex and BF in glaucoma patients, suggestive of compensatory actions in vascular reserve between the two brain regions. The neurovascular coupling within the visual cortex appears deteriorated in glaucoma, whereas the association between BF-visual cortex functional connectivity and rCVR of BF indicates the functional and vascular involvements in glaucoma beyond the primary visual pathway.

Deficiency of phyto-available sulphur, zinc, boron, iron, copper and manganese in soils of India.

Nutrient deficiencies in soil-crop contexts and inappropriate managements are the important reasons for low crop productivity, reduced nutritional quality of agricultural produce and animal/human malnutrition, across the world. The present investigation was carried out to evaluate nutrient deficiencies of sulphur (S) and micronutrients [zinc (Zn), boron (B), iron (Fe), copper (Cu) and manganese (Mn)] in agricultural soils of India for devising effective management strategies to achieve sustainable crop production, improved nutritional quality in crops and better animal/human health. A total of 2,42,827 surface (0-15 cm depth) soil samples were collected from agriculture fields of 615 districts lying in 28 states of India and were analysed for available S and micronutrients concentration. The study was carried out under the aegis of All India Coordinated Research Project on Micro- and Secondary-Nutrients and Pollutant Elements in Soils and Plants. The mean concentrations were 27.0 ± 29.9 mg kg-1 for available S, 1.40 ± 1.60 mg kg-1 for available Zn and 1.40 ± 4.70 mg kg-1 for available B, 31.0 ± 52.2 mg kg-1 for available Fe, 2.30 ± 3.50 mg kg-1 for available Cu and 17.5 ± 21.4 mg kg-1 for available Mn. There were variable and widespread deficiencies of S and micronutrients in different states. The deficiencies (acute deficient + deficient + latent deficiency) of S (58.6% of soils), Zn (51.2% of soils) and B (44.7% of soils) were higher compared to the deficiencies of Fe (19.2% of soils), Cu (11.4% of soils) and Mn (17.4% of soils). Out of 615 districts, > 50% of soils in 101, 131 and 86 districts were deficient in available S, available Zn and available B, respectively. Whereas, > 25% of soils in 83, 5 and 41 districts had deficiencies of available Fe, available Cu and available Mn, respectively. There were occurrences of 2-nutrients deficiencies such S + Zn (9.30% of soils), Zn + B (8.70% of soils), S + B (7.00% of soils) and Zn + Fe (5.80% of soils) to a greater extent compared to the deficiencies of Zn + Mn (3.40% of soils), S + Fe (3.30% of soils), Zn + Cu (2.80% of soils) and Fe + B (2.70% of soils). Relatively lower % of soils were deficient in 3-nutrients (namely S + Zn + B, S + Zn + B and Zn + Fe + B), 4-nutrients (namely Zn + Fe + Cu + Mn) and 5-nutrients (namely Zn + Fe + Cu + Mn + B) simultaneously. The information regarding the distribution of deficiencies of S and micronutrients (both single and multi-nutrients) could be used by various stakeholders for production, supply and application of right kind of fertilizers in different districts, states and agro-ecological regions of India for better crop production, crop nutritional quality, nutrient use efficiency, soil health and for tackling human and animal malnutrition.

Layered Silicate-Alginate Composite Particles for the pH-Mediated Release of Theophylline.

Numerous natural and synthetic clay minerals have proven to be excellent drug carriers for high drug-loaded and sustained release formulations due to their considerable ion exchange, adsorption, and swelling capacities. Moreover, the synthetic smectite clays have added advantages in terms of compositional purity and controlled cation exchange capacity in comparison to natural clays. This study involves the intercalation of theophylline (TP) in a synthetic clay, Laponite® (LP), followed by the inclusion of the resulting intercalates into sodium alginate (SA) beads to achieve pH-controlled drug release. Maximum intercalated drug incorporation of 68 mg/g was obtained by ion exchange at pH 1.2 and confirmed by an increase in basal spacing of the clay from 12.9 to 15.5 Å. TP release from the binary LP-TP intercalates in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was found to be 40% and 70%, respectively. LP-TP particles were also incorporated in an SA matrix via polymer crosslinking using CaCl2(aq) to improve the pH selective release. The ternary polymer-clay-drug composite particles effectively prevented the release of TP at low pH in SGF and resulted in sustained release in SIF, with 40% dissolution within 120 min.

Classification of Pigeonpea (Cajanus cajan (L.) Millsp.) Genotypes for Zinc Efficiency.

Pigeonpea (Cajanus cajan (L.) Millsp.) is grown globally for its protein-rich seed. However, low availability of soil zinc (Zn) adversely affects the seed yield of pigeonpea. The present study was therefore conducted to assess the Zn efficiency of pigeonpea genotypes based on seed yield and seed Zn uptake efficiency. Field experiments were conducted at the Indian Council of Agricultural Research-Indian Institute of Soil Science, Bhopal, India with twenty different pigeonpea genotypes and two levels of Zn application under a split-plot design. The two levels of Zn were low (without application of Zn fertilizer) and high (with application of 20 kg Zn ha-1 (as ZnSO4∙7H2O) as basal soil application, in conjunction with three foliar sprays of 0.50% (w/v) ZnSO4∙7H2O aqueous solution) (with 0.25% lime as neutralizing agent) at flowering, pod formation, and pod filling stages). Application of Zn improved plant height, branches plant-1, pods plant-1, seeds pod-1, and 100 seed weight of pigeonpea genotypes differently. The mean seed yield, seed Zn concentration, and seed Zn uptake of the genotypes increased from 1.71 to 2.12 t ha-1, 32.4 to 43.0 mg kg-1, and 54.9 to 90.6 g ha-1, respectively, with application of Zn. The seed yield efficiency index (SYEI) and Zn uptake efficiency index (ZUEI) of pigeonpea genotypes varied from 67.0 to 92.5 and from 47.0 to 69.9, respectively. Based on SYEI and ZUEI, the genotypes were classified as efficient and responsive (Virsa Arhar-1, GT-1, GT-101, SKNP 05-05, BDN-2, AAUT 2007-04, BSMR 853, T 15-15, DT 23, Pusa 9), efficient and non-responsive (ICPL 87119, PKV Trombay), inefficient and responsive (AKT 8811, Hisar Paras), and inefficient and non-responsive (AAUT 2007-10, JKM 7, Hisar Manak, C 11, Hisar HO2-60, GAUT 93-17). The efficient and responsive genotypes are the most useful as they yield well under low soil Zn conditions and also respond to Zn fertilizer application. The inefficient and responsive genotypes could be utilized for plant breeding programs by plant breeders for identification and utilization of responsive traits.

Investigating multiple sources of data for smart infusion pump and electronic health record interoperability.

PURPOSE: Infusion pump data, which describe compliance to dose-error reduction software among other metrics, are retrievable from infusion pump vendor software, electronic health record (EHR) systems, and regional and national data repositories such as the Regenstrief National Center for Medical Device Informatics (REMEDI). Smart infusion pump and EHR interoperability has added to the granularity and complexity of data collected, and clinicians are challenged with efficiently comprehending and interpreting the data and reports available. SUMMARY: Collaborative partnerships between the Indianapolis Coalition for Patient Safety and the Regenstrief Center for Healthcare Engineering allowed for clinicians, informaticists, researchers, and engineers to compare the information gained and strengths of using smart infusion pumps, EHR, and REMEDI to assess hospital medication safety in a setting of interoperability. Seven reporting capabilities were used to compare available reports, and 2 hypothetical scenarios were developed to highlight these processes. Infusion pump vendor-provided software and reports were found to provide the most usable information for detailed infusion reporting, while the EHR was strongly usable for interoperability compliance and REMEDI excelled in benchmarking capabilities. CONCLUSION: While infusion analytics needs may differ across health systems, a better understanding of the strengths of infusion pump data and EHR data may help provide structure and direction in the infusion analytics process. Infusion data repositories such as REMEDI are useful tools to obtain information in a way not delivered by smart pump data.

Myristic Acid Coated Protein Immobilised Mesoporous Silica Particles as pH Induced Oral Delivery System for the Delivery of Biomolecules.

Solid core drug delivery systems (SCDDS) were prepared for the oral delivery of biomolecules using mesoporous silica as core, bovine haemoglobin (bHb) as model drug and supercritical fluid (SCF) processing as encapsulation technique. The use of organic solvents or harsh processing conditions in the development of drug delivery systems for biomolecules can be detrimental for the structural integrity of the molecule. Hence, the coating on protein-immobilised particles was performed via supercritical carbon dioxide (scCO2) processing at a temperature lower than the melting point of myristic acid (MA) to avoid any thermal degradation of bHb. The SCDDS were prepared by bHb immobilisation on mesoporous silica followed by myristic acid (MA) coating at 43 °C and 100 bar in scCO2. bHb-immobilised silica particles were also coated via solvent evaporation (SE) to compare the protein release with scCO2 processed formulations. In both cases, MA coating provided required enteric protection and restricted the bHb release for the first two hours in simulated gastric fluid (SGF). The protein release was immediate upon the change of media to simulated intestinal fluid (SIF), reaching 70% within three hours. The release from SCF processed samples was slower than SE formulations, indicating superior surface coverage of MA on particles in comparison to the SE method. Most importantly, the protein conformation remained unchanged after the release from SCDDS as confirmed by circular dichroism. This study clearly demonstrates that the approach involving protein immobilisation on silica and scCO2 assisted melt-coating method can protect biomolecules from gastric environment and provide the required release of a biologic in intestine without any untoward effects on protein conformation during processing or after release.