Application of disaccharides alone and in combination,for the improvement of stability and particle properties of spray-freeze dried IgG

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.

Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.

Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.

Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules.     

A case of group A streptococcal meningitis following acute otitis media.

Group A streptococcal meningitis is less common than other forms of meningitis; however, the occurrence of this infection is associated with high mortality and morbidity. Early recognition and a prompt treatment are therefore essential. We review one case of an Asian women admitted with group A streptococcal meningitis as a complication of otitis media.     

To screen or not to screen? The development of a prediction model for aorto-iliac stenosis in kidney transplant candidates

Screening for aorto-iliac stenosis is important in kidney transplant candidates as its presence affects pre-transplantation decisions regarding side of implantation and the need for an additional vascular procedure. Reliable imaging techniques to identify this condition require contrast fluid, which can be harmful in these patients. To guide patient selection for these imaging techniques, we aimed to develop a prediction model for the presence of aorto-iliac stenosis. Patients with contrast-enhanced imaging available in the pre-transplant screening between January 1st, 2000 and December 31st, 2018 were included. A prediction model was developed using multivariable logistic regression analysis and internally validated using bootstrap resampling. Model performance was assessed with the concordance index and calibration slope. Three hundred and seventy-three patients were included, 90 patients (24.1%) had imaging-proven aorto-iliac stenosis. Our final model included age, smoking, peripheral arterial disease, coronary artery disease, a previous transplant, intermittent claudication and the presence of a femoral artery murmur. The model yielded excellent discrimination (optimism-corrected concordance index: 0.83) and calibration (optimism-corrected calibration slope: 0.91). In conclusion, this prediction model can guide the development of standardized protocols to decide which patients should receive vascular screening to identify aorto-iliac stenosis. External validation is needed before this model can be implemented in patient care.     

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients.MethodsData were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test.ResultsSixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored.ConclusionsSevere disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.     

Supportive care in a patient with Alstrom syndrome with hyperphenylalaninemia and sleep problems

Alstrom syndrome is a rare genetic disorder with an autosomal recessive mutation in the ALMS1 gene. The disease''s manifestations include ophthalmic problems, hearing loss, obesity, and cardiovascular disorders. In addition, medical cases include other organ complications. However, the overlapping variety of such symptoms with other diseases may delay the diagnosis. In this article, we describe the case of a 7‐year‐old female patient with Alstrom syndrome, and cardiovascular and hyperphenylalaninemia diseases since birth. Other symptoms included diabetes and ophthalmologic problems with skeletal disability. Blindness and hearing impairment were diagnosed, along with recurrence of respiratory problems at the age of 7 years. The patient''s obesity‐induced snoring predisposed her to uncontrolled blood glucose. In fact, respiratory tract problems and sleep disorders had occurred as a degraded cycle and left her with a severe disability for years. The similarity of the symptoms with other diseases had misled the physician in diagnosis. However, a polysomnography test (because of complaints of short sleep duration) recognized the source of the patient''s sleep disorders and breathing problems. Eventually, we delivered a portable ventilator to the child for continuous positive airway pressure (CPAP) therapy. The child''s breathing and oxygenation conditions improved. Using the ventilator and the CPAP system, we discharged her from the hospital without requiring oxygenation, in a stable condition. The procedure could prevent the patient from hypoxia and retinal problem.     

Clinical aspects of infertile 47,XYY patients: a retrospective study

47,XYY syndrome is a sex chromosomal anomaly in men, which may be associated with infertility and has an incidence of 0.1% of male births. The clinical and paraclinical characteristics of men suffering from this anomaly have not been fully described. In this retrospective study, we present 37 cases of 47,XYY infertile men with sperm counts varying from normal to azoospermia, referred to the Genetics Laboratory at the Royan Institute, Iran. Thirteen individuals were mosaic and 24 non-mosaics. Non-mosaic patients were classified as azoospermic (nine cases) and normospermic/oligozoospermic men (15 cases). Two of the non-mosaic and three mosaic patients had secondary infertility. In addition, 13 of them underwent IUI, IVF or ICSI, and in seven cases, there was a biochemical pregnancy. The remaining 14 patients did not have ART. The 47,XYY syndrome is relatively unusual and can be missed clinically because of the lack of symptoms and of diverse phenotypes. Diagnosis of this aneuploidy can provide valuable data for counselling and early management of the patients who undergo fertility evaluation.     

Developmental toxicity of deltamethrin and 3-phenoxybenzoic acid in embryo–larval stages of zebrafish (Danio rerio)

Synthetic pyrethroids are the major insecticides used widely in agriculture and household pest control. Deltamethrin (DM), a widely used type II pyrethroid insecticide, is a relatively potent neurotoxicant. 3-Phenoxybenzoic acid (PBA) is the major metabolite formed due to metabolism of DM. In order to illustrate the toxic response of zebrafish embryos/larvae to DM and PBA the present research was carried out. For this 4hpf embryos were treated with two concentrations of DM (100 and 200?μg/L) for 48?h and PBA (1000 and 2000?μg/L) for 96?h or 99.9% ethanol (solvent control). Early life stage parameters were observed at specified time points. DM-treated embryo/larvae exhibited increased mortality, delay in hatching time, decrease in percentage of hatched embryos, increase of heartbeat rate and decrease in blood flow; lightening of body and eye pigmentation in a dose dependent manner. Pericardial and yolk sac edema along with were also caused by DM. Along with these crooked notochord, tail deformation was noticed in hatched and unhatched embryos. In case of PBA treated embryos and larvae, increased embryos/larvae length and yolk sac size were observed. Other abnormalities like edema (yolk sac and pericardial), decreased eye and body pigmentation were also observed but in some embryos only. These were not as severe as observed in parental compound indicating that DM is more toxic than its metabolite PBA. The data contributes to a better understanding of the potential consequences of fish exposed to DM and PBA.     

Evaluation of Non Diseased Specified Outcome Measures in Hand Injuries to Assess Activity and Participation Based on ICF Content

The objective of the study is to provide information about non disease specified outcome measures which evaluate disability in patients who have impairments in hand and upper extremity and to find the extent to which they are evaluating “disability” based on ICF hand Core Set (activity limitation and participation restriction). MEDLINE, CINAHL, GOOGLE SCHOLAR , OVID and SCIENCE DIRECT databases were systematically searched for studies on non disease specified outcome measures used to evaluate upper extremity function; only studies written in English were considered. We reviewed titles and abstracts of the identified studies to determine whether the studies met predefined eligibility criteria (eg, non disease specified out come measures used in hand injured patients). All the outcome measures which had eligibility included. After full text review ,7 non disease specified outcome measures in hand were identified. Studies were extracted, and the information retrieved from them. All the outcome measures which had incuded, were linked with ICF hand core set disability part (activity and participation). All of them only linked to 16 (42 %) components of ICF hand Core Set, which were most activity and less participation from ICF. None of the non disease specified out come measures in hand injuries cover all domains of disability from the ICF Hand Core Set.