The influence of Age of Onset (AO) of Second Language Acquisition (SLA) on learners‟ Ultimate Attainment (UA) potential is well documented. The issue of Second Language Acquisition (SLA) potential enters a qualitatively different, pragmatic dimension in most multilingual developing nations (including Papua New Guinea), where English, a second language for most children, is also the language of education, and where, consequently, students‟ English proficiency necessarily affects their academic potential and the quality of their education. This study investigates whether the academic performance of students in the School of Humanities and Social Sciences (SHSS) University of Papua New Guinea (UPNG) is affected by their linguistic backgrounds. Specifically, we examined the effect of three factors in the students‟ Early Language Education – their Age of Onset of learning English (AO), their Age at Literacy (AGELIT), and their Early Learning Language (ELL) – on their Semester 1, 2017 Grade Points Average (GPA). A purposive cross-sectional sampling method was used for the selection of students. All full-time registered students in the SHSS during the 2017 academic session were eligible to participate in the study. A self-designed pretested questionnaire consisting of nine short questions was used to collect data on SHSS students‟ language education backgrounds, including their AO, AGELIT and ELL. Our results show a strong and statistically significant inverse correlation between students‟ AO/AGELIT and their GPAs, as well as a strong positive link between ELL English and students‟ GPAs, which contrasts sharply with a significant decrease in GPAs in the presence of ELL Tok Pisin. The ELL Vernacular category was too small (sample size N=34) to yield statistically significant results. Our current results corroborate the findings of our earlier studies which established a highly significant inverse correlation between students‟ AO and their academic performance in the National High Schools, as well as in the University of Papua New Guinea.

BACKGROUND: Tension pneumothorax (TPX) is an uncommon but life-threatening condition. It is important that this uncommon presentation, managed by needle decompression, is practised by paramedics using a range of educationally sound and realistic mannequins. The objective of this study is to identify if the chest wall thickness (CWT) of training mannequins used for chest decompression is an anatomically accurate representation of a human chest. METHODS: This is a two-part study. A review of the literature was conducted to identify chest wal thickness in humans and measurement of chest wal thickness on two commonly used mannequins. The literature search was conducted using the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, and EMBASE databases from their beginning until the end of May 2012. Key words included chest wall thickness, tension pneumothorax, pneumothorax, thoracostomy, needle thoracostomy, decompression, and needle test. Studies were included if they reported chest wal thickness. RESULTS: For the literature review, 4461 articles were located with 9 meeting the inclusion criteria. Chest wall thickness in adults varied between 1.3 cm and 9.3 cm at the area of the second intercostal space mid clavicular line. The Laerdal? manikin in the area of the second intercostal space mid clavicular line, right side of the chest was 1.1 cm thick with the left 1.5 cm. The MPL manikin in the same area or on the right side of the chest was 1.4 cm thick but on the left 1.0 cm. CONCLUSION: Mannequin chests are not an accurate representation of the human chest when used for decompressing a tension pneumothorax and therefore may not provide a realistic experience.

Intraganglionic laminar endings (IGLEs) have been supposed to be the mechanoreceptors in the gut by electrophysiological recording techniques. But the specialized morphology of IGLEs could not be displayed closely associated with this function and the mechanism that IGLEs act as the mechanotransduction sites in the gut is not yet well understood. In the present study, we used styryl dye FM1-43 combined with stretch stimulation in the guinea pig esophagus to test whether IGLEs acted as the mechano-sensitive receptors of the vagal afferent nerves. At the same time, the special structure of IGLEs displayed by FM1-43 was further confirmed by neurobiotin anterograde labeling technique. To further investigate the characteristics of IGLEs as mechanosensitive receptors, different drugs were used to block or stimulate IGLEs activation. Our results indicated that only in the stretched preparation could FM1-43 enter the IGLEs and completely display their specialized structure, which was consistent with that shown by neurobiotin. The amount of IGLEs shown by stretch-evoked FM1-43 staining was much more than that shown without stretch stimulation [(90.4 +/- 9.5) % vs (10.7 +/- 2.1) %, P<0.05]. Ca(2+), TTX (0.6 mumol/L), atropine (0.6 mumol/L), SKF (50 mumol/L), and gadolium (100 mumol/L) had no effect on the IGLEs activation. But for benzamil (100 mumol/L), an epithelial sodium channel blocker, activation of IGLEs by stretch stimulation was significantly blocked. The potent ATP analogue, alpha,beta-methylene ATP (100 mumol/L) could not activate FM1-43 staining without stretch. These results indicate that IGLEs are sensitive to mechanical stimulation. This could lead to the deduction that IGLEs act as the mechanoreceptors of vagal afferent nerve. IGLEs could transmit mechanical stimuli directly through ion channels, independent of neurotransmitter release and action potential propagation. The stretch-sensitive channels on IGLEs probably belong to the epithelial sodium channel family rather than voltage-gated sodium ion channels. Furthermore, styryl dye FM1-43 is a useful activity-dependent marker to demonstrate the structure and function of IGLEs in guinea pig esophagus.
Afferent Pathways ; physiology ; Animals ; Esophagus ; innervation ; Female ; Ganglia, Autonomic ; physiology ; Guinea Pigs ; Male ; Mechanoreceptors ; physiology ; Nerve Endings ; physiology ; Vagus Nerve ; physiology

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75%relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.

Dural arteriovenous fistulas (DAVF) are rare acquired lesions resulting from abnormal shunting between intracranial dural arteries and venous system. Typically arising from structural weakness of the dura and a coinciding trigger factor, DAVFs can present with similar clinical and imaging characteristics to sinus thrombosis. A 61-year-old male with a history of meningioma previously managed with subtotal resection and stereotactic radiosurgery presented with progressive right-sided vision loss and bilateral papilledema. Initial imaging suggested possible sinus occlusion. Catheter angiogram revealed a Borden-Shucart grade III DAVF of the superior sagittal sinus and elevated venous pressures and the patient subsequently underwent endovascular transarterial intervention twice. We report on the first case of a superior sagittal sinus DAVF occurring after surgical resection of a parasagittal meningioma.

Dural arteriovenous fistulas (DAVF) are rare acquired lesions resulting from abnormal shunting between intracranial dural arteries and venous system. Typically arising from structural weakness of the dura and a coinciding trigger factor, DAVFs can present with similar clinical and imaging characteristics to sinus thrombosis. A 61-year-old male with a history of meningioma previously managed with subtotal resection and stereotactic radiosurgery presented with progressive right-sided vision loss and bilateral papilledema. Initial imaging suggested possible sinus occlusion. Catheter angiogram revealed a Borden-Shucart grade III DAVF of the superior sagittal sinus and elevated venous pressures and the patient subsequently underwent endovascular transarterial intervention twice. We report on the first case of a superior sagittal sinus DAVF occurring after surgical resection of a parasagittal meningioma.

Circadian disruption is being increasingly recognized as a critical factor in the development and progression of Parkinson’s disease (PD). This review aims to provide an in-depth overview of the relationship between circadian disruption and PD by exploring the molecular, cellular, and behavioral aspects of this interaction. This review will include a comprehensive understanding of how the clock gene system and transcription–translation feedback loops function and how they are diminished in PD. The article also discusses the role of clock genes in the regulation of circadian rhythms, as well as the impact of clock gene dysregulation on mitochondrial function, oxidative stress, and neuroinflammation, including the microbiota-gut-brain axis, which have all been proposed as being crucial mechanisms in the pathophysiology of PD. Finally, this review highlights potential therapeutic strategies targeting the clock gene system and circadian rhythm for the treatment of PD.

We have previously described a novel artificial NFEV β-secretase (BACE1) cleavage site, which when introduced into the amyloid-β precursor protein (APP), significantly enhances APP cleavage by BACE1 in in vitro and cellular assays. In this study, we describe the identification and characterization of a single chain fragment of variable region (scFv), specific to the EV neo-epitope derived from BACE1 cleavage of the NFEV-containing peptide, and its conversion to IgG1. Both the scFv displayed on phage and EV-IgG1 show exquisite specificity for binding to the EV neoepitope without cross-reactivity to other NFEV containing peptides or WT-APP KMDA cleavage products. EV-IgG1 can detect as little as 0.3 nmol/L of the EV peptide. EV-IgG1 antibody was purified, conjugated with alkaline phosphatase and utilized in various biological assays. In the BACE1 enzymatic assay using NFEV substrate, a BACE1 inhibitor MRK-3 inhibited cleavage with an IC(50) of 2.4 nmol/L with excellent reproducibility. In an APP_NFEV stable SH-SY5Y cellular assay, the EC(50) for inhibition of EV-Aβ peptide secretion with MRK-3 was 236 nmol/L, consistent with values derived using an EV polyclonal antibody. In an APP_NFEV knock-in mouse model, both Aβ_EV40 and Aβ_EV42 peptides in brain homogenate showed excellent gene dosage dependence. In conclusion, the EV neoepitope specific monoclonal antibody is a novel reagent for BACE1 inhibitor discovery for both in vitro, cellular screening assays and in vivo biochemical studies. The methods described herein are generally applicable to novel synthetic substrates and enzyme targets to enable robust screening platforms for enzyme inhibitors.
Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; chemistry ; genetics ; Amyloid beta-Protein Precursor ; Animals ; Antibodies ; pharmacology ; Brain Chemistry ; drug effects ; Disease Models, Animal ; Enzyme Inhibitors ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Gene Knock-In Techniques ; Humans ; Inhibitory Concentration 50 ; Mice ; Molecular Sequence Data ; Single-Chain Antibodies ; pharmacology

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.