Atypical manifestation of a fistula between a hydatid cyst of a liver and a gallbladder: A case report

The hydatid cyst of the liver is the most common location of hydatid disease. Complications in this form are dominated by superinfection of the cyst and rupture into the bile ducts or the peritoneal cavity. We report the case of a 54-year-old female patient with a hydatid cyst of the liver complicated by a rupture in the gallbladder revealed by urinary symptoms.     

Fractal Analysis of a Non-Newtonian Fluid Flow in a Rough-Walled Pipe

The fully developed laminar flow of a viscous non-Newtonian fluid in a rough-walled pipe is considered. The fluid rheology is described by the power–law model (covering shear thinning, Newtonian, and shear thickening fluids). The rough surface of the pipe is considered to be fractal, and the surface roughness is measured using surface fractal dimensions. The main focus of this study lies in the theoretical investigation of the influence of the pipe surface roughness on the velocity profile and the Darcy friction factor of an incompressible non-Newtonian fluid. The plotted results demonstrate that shear thinning fluids are the most sensitive to the surface roughness compared with Newtonian and shear thickening fluids. For a particular value of the surface fractal dimension, there exists an intersection point where shear thinning, Newtonian, and shear thickening fluids behave the same way regarding the amplitude of the velocity profile and the friction factor. This approach has a variety of potential applications, for instance fluid dynamics in hydrology, blood flow in the cardiovascular system, and many industrial applications.     

Software-Automated Implant Detection for Intraoperative 3D Imaging—First Clinical Evaluation on 214 Data Sets

Previous studies have demonstrated a frequent occurrence of screw/K-wire malpositioning during surgical fracture treatment under 2D fluoroscopy and a correspondingly high revision rate as a result of using intraoperative 3D imaging. In order to facilitate and accelerate the diagnosis of implant malpositioning in 3D data sets, this study investigates two versions of an implant detection software for mobile 3D C-arms in terms of their detection performance based on comparison with manual evaluation. The 3D data sets of patients who had received surgical fracture treatment at five anatomical regions were extracted from the research database. First, manual evaluation of the data sets was performed, and the number of implanted implants was assessed. For 25 data sets, the time required by four investigators to adjust each implant was monitored. Subsequently, the evaluation was performed using both software versions based on the following detection parameters: true-positive-rate, false-negative-rate, false-detection-rate and positive predictive value. Furthermore, the causes of false positive and false negative detected implants depending on the anatomical region were investigated. Two hundred fourteen data sets with overall 1767 implants were included. The detection parameters were significantly improved (p<.001) from version 1 to version 2 of the implant detection software. Automatic evaluation required an average of 4.1±0.4 s while manual evaluation was completed in 136.15±72.9 s (p<.001), with a statistically significant difference between experienced and inexperienced users (p=.005). In summary, version 2 of the implant detection software achieved significantly better results. The time saved by using the software could contribute to optimizing the intraoperative workflow.     

Hemangioma of the maxillary sinus: A benign and rare cause of epistaxis

Hemangioma of the facial sinuses is a rare pathology, and given the lack of clinical specificity, the differential diagnosis with a malignant lesion often arises. We report the case of a 32-year-old patient who consulted for recurrent epistaxis of moderate severity. The preoperative diagnosis of a hemangioma of the left maxillary sinus was based on computed tomography and magnetic resonance imaging data, confirmed by the anatomopathological study of the surgical specimen, preceded by an embolization that facilitated the endoscopic surgical excision.     

Occurrence of <Emphasis Type="Italic">Demodex</Emphasis> species in patients with blepharitis and in healthy individuals: a 10-year observational study

Purpose

Two Demodex species (eyelash mites)—D. folliculorum and D brevis—are believed to be associated with human skin and eye diseases. However, the clinical significance of infection with Demodex species remains controversial.

Study design

The aim of this study was to estimate the prevalence of ocular demodicosis in patients with blepharitis as compared with the prevalence in the healthy population in Poland.

Methods

This case-control prospective study was carried out from 2007 to 2016. The enrolled patients (668) were divided into 2 groups: the study group, comprising 553 patients with blepharitis (349 women and 204 men, aged 17–88 years), and the control group, comprising 115 healthy volunteers without a history of ocular pathologies (78 women and 37 men, aged 17–88 years). A sample of 10 eyelashes was taken aseptically from each eye of the examined person and later studied under a light microscope.

Results

Demodex species were found in 62.4% (345/544) of the patients in the study group and in 24.3% (28/100) of the controls (P = .001, OR = 0.006). The overall prevalence was 55.8% (373/668) in all the examined participants. The presence of Demodex infection increased with age in both groups. No association of Demodex infection with gender was found (119/204 vs 226/349; P > .05, OR 1.086). A high mean number of mites was present more frequently in patients aged older than 50 years and in those who complained especially about itching (P < .05).

Conclusion

The prevalence of ocular demodicosis is significantly correlated with blepharitis and increases with age.

     

PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid^® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid^® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid^® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid^® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits’ eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C_max and AUC_0–24-values, respectively, compared to the drug suspension. PLGA-modified Syloid^® microparticles represent a potential option to augment the bioavailability of ocular drugs.     

Modeling and Control of Layer Height in Laser Wire Additive Manufacturing

Laser Wire Additive Manufacturing (LWAM) is a flexible and fast manufacturing method used to produce variants of high metal geometric complexity. In this work, a physics-based model of the bead geometry including process parameters and material properties was developed for the LWAM process of large-scale products. The developed model aimed to include critical process parameters, material properties and thermal history to describe the relationship between the layer height with different process inputs (i.e., the power, the standoff distance, the temperature, the wire-feed rate, and the travel speed). Then, a Model Predictive Controller (MPC) was designed to keep the layer height trajectory constant taking into consideration the constraints faced in the LWAM technology. Experimental validation results were performed to check the accuracy of the proposed model and the results revealed that the developed model matches the experimental data. Finally, the designed MPC controller was able to track a predefined layer height reference signal by controlling the temperature input of the system.     

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β₂-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.     

A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide,ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours

Background We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide.Methods We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours.Results Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10–300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1–2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3–18) weeks. Four of 18 evaluable patients (22%) had stable disease.Conclusions Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.Subject terms: Drug development, Drug safety