Exploring light-emitting diode pumped luminescent concentrators in solid-state laser applications.

In the past, there were limited efforts to use light-emitting diodes (LEDs) for pumping solid-state lasers. However, these attempts were overshadowed by the introduction of laser diodes, which offered more favourable pumping conditions. Nevertheless, recent advancements in high-power LEDs, coupled with the utilization of luminescent concentrators (LC), have paved the way for a novel approach to pump solid-state lasers. The combination of LEDs and LC in this LED-LC system presents several advantages, including enhanced ruggedness, stability, and cost-effectiveness compared to other laser pumping methods. This review explores the various techniques employed to pump solid-state lasers using LED-LC as a pump source, along with improvements made to enhance the brightness of LEDs in this context.

Synthesis of an eco-inspired anticorrosive composite for mild steel applications.

We synthesised a polyaniline/mica (Mica-PANI) nanocomposite using naturally occurring muscovite mica by a top-down approach. The developed coating materials were characterised using a different technique to investigate their chemical and structural properties using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Furthermore, the electrochemical properties of the coating materials were investigated by linear sweep voltammetry (LSV). SEM images elucidate the composite's average particle diameter of the prepared nano-mica, approximately 80 nm. The existence of relevant functional groups and bonding in the prepared Mica-PANI composite material was confirmed by means of XPS and FTIR techniques. Moreover, the synthesised composite with 5% w/w shows high anticorrosion protection, i.e. 84 µm per year, compared to competing materials, including commercial paint and individual raw materials (0.35 mm per year). The anti-corrosive effect occurs mainly due to two opposing effects: the formation of an Fe(OH)3 passive layer on the steel surface by oxidation of surface iron atoms by the PANI and the barrier effect of mica NPs through inhibition of corrosive agents. Therefore, the eco-inspired composite could be an ideal cost-effective coating material to prevent the corrosion of mild steel surfaces.

Prevalence of pretreatment drug resistance in persons initiating and reinitiating antiretroviral therapy in Sri Lanka: results from a national representative survey.

BACKGROUND: We conducted a nationwide cross-sectional study to estimate pretreatment drug resistance (PDR) prevalence in adults initiating ART in Sri Lanka following the WHO's recommendations. METHODS: HIV drug resistance was determined on dried blood spots (DBSs) using population-based sequencing of the protease and reverse transcriptase genes and interpretation was based on Stanford HIVdb v9.0. Analyses were weighted to adjust for multistage sampling and genotypic failure rate. We used logistic regression to assess differences between groups. RESULTS: Overall, in 10% (15 of 150) of patients initiating ART, HIV drug resistance mutations were detected. The prevalence of resistance to NNRTI drugs efavirenz/nevirapine was 8.4% (95% CI 4.6-15.0) but differed among those reporting having prior antiretroviral (ARV) exposure (24.4%, 95% CI 13.8-39.5) compared with 4.6% (95% CI 1.6-12.8) for those reporting as being ARV naive (OR 4.6, 95% CI 1.3-16.6, P = 0.021). PDR to efavirenz/nevirapine was also nearly twice as high among women (14.1%, 95% CI 6.1-29.4) compared with men (7.0%, 95% CI 3.1-14.7) (P = 0.340) and three times high among heterosexuals (10.4%, 95% CI 2.4-35.4) compared with MSM (3.8%, 95% CI 1.1-12.7) (P = 0.028). NRTI PDR prevalence was 3.8% (95% CI 1.1-12.1) and no PI PDR was observed in the study. CONCLUSIONS: A high prevalence of efavirenz/nevirapine PDR was reported, especially in patients with prior ARV exposure, in women and those reporting being heterosexual. These findings highlight the need to fast-track the transition to the WHO-recommended dolutegravir-based first-line ART.

Probing the Interfacial Interactions of Monoclonal and Bispecific Antibodies at the Silicone Oil-Aqueous Solution Interface by Using Sum Frequency Generation Vibrational Spectroscopy.

Silicone oil has been widely utilized in the pharmaceutical industry especially as a lubricant coating commonly used in syringes for the smooth delivery of drugs. Protein structure perturbation and aggregation have been reported upon protein contacting silicone oil by using indirect methods and ex-situ techniques. The conclusions derived from such indirect and ex-situ methods may not truly reflect the exact nature of the protein-silicone oil interfacial interactions. Recently, we have successfully demonstrated that sum frequency generation (SFG) vibrational spectroscopy can be used as a powerful and direct method of studying the fusion protein-silicone oil interfacial interactions in situ and in real time. In this article, we studied monoclonal and bispecific antibody interactions with the silicone oil surface by using SFG spectroscopy. Being structurally and functionally different in the nature of fusion proteins and antibodies, this study is important in enhancing our current understanding of protein-silicone oil interfacial interactions. Both types of antibodies investigated here readily and strongly adsorb onto the silicone oil surface and remain stable at least for 10 h. SFG spectra in the amide I region for monoclonal and bispecific antibodies centered at 1660 and 1665 cm-1, respectively, suggest the difference in their molecular structures. The absence of the antibody signals in the amide I region of time-dependent and static SFG spectra obtained for preadsorbed antibodies onto silicone oil after contacting polysorbate 80 (PS-80) surfactant suggests that PS-80 can effectively remove both types of antibodies from the silicone oil surface. This study demonstrated the feasibility of using SFG spectroscopy as a powerful tool for probing the antibody-interfacial interactions in situ and in real time.

Severe Disabling Myalgia as an Initial Presentation of Polyarteritis Nodosa.

BACKGROUND: Polyarteritis nodosa (PAN) is a form of necrotizing vasculitis affecting medium or small blood vessels with multiorgan involvement. Although myalgia is a clinical feature of PAN, severe disabling myalgia as the initial presentation is rarely noted. CASE PRESENTATION: We present a case of 54-year-old male with recently detected chronic kidney disease admitted with progressive severe disabling muscular pains predominantly over calves with constitutional symptoms for seven weeks. He was weak to mobilize out of the bed. Later, he developed a vasculitic rash, unilateral ulnar claw, and bilateral foot drop. His skin and muscle biopsies showed evidence of vasculitis. His renal and mesenteric artery CT angiogram revealed stenosed segment of the celiac artery without evidence of visible aneurysms elsewhere. He completed six cycles of intravenous cyclophosphamide pulse therapy with high-dose oral prednisolone with good response. With continuation of aggressive immunosuppression and rehabilitation for five months, the patient improved and was able to walk without support. CONCLUSION: Musculoskeletal predominant PAN, even though rare, needs to be considered in patients presenting with disabling muscle pain and weakness. These features may herald over days to months along with constitutional symptoms before other systems getting affected. Early recognition of such symptoms and initiating specific treatment would be important for better outcomes.

Prevalence of Fragile X Syndrome among children receiving special education and carrier states in first degree relatives.

Introduction: Fragile X syndrome (FXS) is a genetically determined developmental disorder. Underlying genotype is cytosine-guanine-guanine (CGG) repeat expansions with over 200 repeats in the fragile X mental retardation 1 (FMR1) gene. Children with FXS are most accessible in special education institutions in Sri Lanka, with a total of approximately 6000 registered attendees. Objectives: The aim of the current study was to estimate the prevalence of FXS among special school attendees and to screen first degree relatives of affected children. Methods: A nationally representative sample of 850 children (5-18 years) was selected using multi-level stratified sampling. Screening was performed by 3' direct triplet primed PCR, followed by melting curve analysis. Expanded repeat status of the screened positives were confirmed using capillary electrophoresis, methylation specific PCR and Southern hybridization. Screening of available first degree relatives (n=12) were carried out using the same method of screening and diagnosis. Results: Eleven had FXS. Prevalence of FXS was 1.3% (95% CI 0.9-1.6). Among the 11 with FXS 9 had more than 350 CGG repeats, while the rest had around 300. Twelve first degree relatives consisting of nine mothers, two female siblings and a male sibling were tested. All mothers and female siblings had either full mutation or premutation while the male sibling had CGG repeats in the normal range. Conclusions: Among the special school attendees, prevalence of FXS was 1.3% which has a high risk for autism and attention deficit hyperactivity disorder.

Recent translational research into targeted therapy for liposarcoma.

Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates. Tyrosine kinase inhibitors targeting MET, AXL, IGF1R, EGFR, VEGFR2, PDGFR-ß and Aurora kinase are effective in certain types of LPS. Abnormalities in the PI3K/Akt signaling pathway deregulation of C/EBP-α and its partner PPAR-γ, and the interaction between calreticulin (CRT) and CD47 are also promising therapeutic targets. These promising new approaches may help to supplement existing treatments for LPS.

Validation of the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) in two south- Asian languages.

INTRODUCTION: The multifaceted nature of pelvic floor disorders means that a systematic evaluation is required for optimal treatment outcome. It is also generally acknowledged that a valid tool is necessary to objectively assess symptoms reported by affected women. METHODS: The International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) questionnaire was translated to Sinhala and Tamil and a validation study carried out among women attending gynecology clinics at North Colombo Teaching Hospital, Ragama, and the district general hospitals Mannar and Vavuniya. RESULTS: Content validity was assessed by the level of missing answers, which was < 4% and 2% for each item in Sinhala and Tamil, respectively. Construct validity was assessed by the ability of the questionnaire to differentiate between patients and controls. Both differentiated patients from controls on vaginal symptoms score (VSS) (p < 0.001), sexual symptoms score (SSS) (p < 0.01), and quality of life (QoL) (p < 0.001). There was a strong positive correlation between Pelvic Organ Prolapse Quantification (POP-Q) scores and VSS (Sinhala r s = 0.64, p < 0.001, Tamil r s = 0.65, p < 0.001), and QoL (Sinhala r s = 0.49, p < 0.001, Tamil r s = 0.60, p < 0.001). Internal consistency as assessed using Cronbach's coefficient alpha: 0.78 (0.76-0.78) and 0.83 (0.80-0.84) in Sinhala and Tamil, respectively. Test-retest reliability was assessed by weighted kappa scores (Sinhala 0.58-0.88 and Tamil 0.76-0.90). Both questionnaires were sensitive to change and showed that VSS and QoL improved following surgery (Wilcoxon matched-pairs signed-rank test p < 0.001). CONCLUSION: The validated Sinhala and Tamil translations of ICIQ-VS will be useful for assessing vaginal and sexual symptoms among women speaking Sinhala and Tamil.

Forensic age estimation in anti-piracy trials in Seychelles: Experiences and challenges faced.

Forensic age estimation (FAE) was conducted using a multifactorial method on thirteen Somali detainees claiming juvenile status during the anti-piracy trials of the Seychelles Supreme Court in 2014/2015. A multidisciplinary team, comprising of four of the authors covering specialties in forensic medicine, forensic odontology and radiology, conducted the FAE using a five-stage protocol. Each detainee was interviewed with an interpreter and examined for disorders affecting dental/skeletal development and for assessment of genital development through Tanner staging. Dental maturity was assessed clinically and radiologically. Eruption stage was assessed using Olze et al. and mandibular third-molar maturity was assessed using Demirjian's classification. Skeletal maturity was assessed from hand-wrist X-rays according to Greulich & Pyle and from CT-clavicle according to Kellinghaus et al. and Schultz et al. Interpretation of findings was done using reference population data from similar ethnic and social backgrounds wherever possible. Final age-ranges were calculated by combining dental and clavicle maturity stages using the regression formula developed by Bassed et al. followed by a 10% correction factor. The team later testified on their findings under cross-examination. The protocol adopted by the authors increased the scientific validity of the findings and was useful in addressing cross-examination queries on exclusion of developmental disorders, ethnic/socioeconomic variability and maintaining chain of custody. Unforeseen jurisdictional and practical limitations were experienced but did not affect the outcome. Combining dental and clavicle developmental data provided the court with a much clearer picture on the likelihood of the detainees' juvenile status which emphasizes the importance of conducting more population studies using combinations of different developmental sites. The authors note that available reference data is mostly from affluent populations whereas FAE is mostly required in individuals from less-developed regions. Regional networks that collate and share population-specific data need to be established to overcome these limitations.

Molecular basis of kindlin-2 binding to integrin-linked kinase pseudokinase for regulating cell adhesion.

Integrin-linked kinase (ILK) is a distinct intracellular adaptor essential for integrin-mediated cell-extracellular matrix adhesion, cell spreading, and migration. Acting as a major docking platform in focal adhesions, ILK engages many proteins to dynamically link integrins with the cytoskeleton, but the underlying mechanism remains elusive. Here, we have characterized the interaction of ILK with kindlin-2, a key regulator for integrin bidirectional signaling. We show that human kindlin-2 binds to human ILK with high affinity. Using systematic mapping approaches, we have identified a major ILK binding site involving a 20-residue fragment (residues 339-358) in kindlin-2. NMR-based analysis reveals a helical conformation of this fragment that utilizes its leucine-rich surface to recognize the ILK pseudokinase domain in a mode that is distinct from another ILK pseudokinase domain binding protein, α-parvin. Structure-based mutational experiments further demonstrate that the kindlin-2 binding to ILK is crucial for the kindlin-2 localization to focal adhesions and cell spreading (integrin outside-in signaling) but dispensable for the kindlin-2-mediated integrin activation (integrin inside-out signaling). These data define a specific mode of the kindlin-2/ILK interaction with mechanistic implications as to how it spatiotemporally mediates integrin signaling and cell adhesion.

Role of red cell distribution width in screening for Hb E trait in population screening for hemoglobin disorders.

The national screening policy for hemoglobinopathies uses the cutoffs for red cell indices mean corpuscular volume >80 and mean corpuscular hemoglobin >27, a strategy known to miss some individuals with Hb E trait (EBT), the most common abnormal hemoglobin in Sri Lanka. We wanted to determine if red cell distribution width (RDW) cutoff values would help in increasing the sensitivity of screening for Hb E trait. High-performance liquid chromatography was carried out as the gold standard to detect hemoglobinopathies and red blood cell parameters with colter counter. Receiver operating characteristic curve was drawn to determine the cutoff value for EBT against ß-trait (BTT) and other anemias. Of the 504 patients, 246 had BTT, 110 had EBT, and 151 had other types of anemias. Mean (SD) RDW among patients with BTT was 16 (2.8), with EBT 14.5 (2.9), and with other anemias 15.8 (4.2) (P>0.001). With 14.45 as the cutoff for RDW and considering accepted values for mean corpuscular volume >80 and mean corpuscular hemoglobin >27, it gave a predictive sensitivity of 98.2% for EBT. By using RDW cutoff at 14.45 in addition to the accepted screening indices, sensitivity of Hb E trait detection went up to 98.2% from 86.6%. This study highlights the importance of taking RDW into consideration for screening.

Spatial coordination of kindlin-2 with talin head domain in interaction with integrin ß cytoplasmic tails.

Both talin head domain and kindlin-2 interact with integrin ß cytoplasmic tails, and they function in concert to induce integrin activation. Binding of talin head domain to ß cytoplasmic tails has been characterized extensively, but information on the interaction of kindin-2 with this integrin segment is limited. In this study, we systematically examine the interactions of kindlin-2 with integrin ß tails. Kindlin-2 interacted well with ß(1) and ß(3) tails but poorly with the ß(2) cytoplasmic tail. This binding selectivity was determined by the non-conserved residues, primarily the three amino acids at the extreme C terminus of the ß(3) tail, and the sequence in ß(2) was non-permissive. The region at the C termini of integrin ß(1) and ß(3) tails recognized by kindlin-2 was a binding core of 12 amino acids. Kindlin-2 and talin head do not interact with one another but can bind simultaneously to the integrin ß(3) tail without enhancing or inhibiting the interaction of the other binding partner. Kindlin-2 itself failed to directly unclasp integrin α/ß tail complex, indicating that kindlin-2 must cooperate with talin to support the integrin activation mechanism.

A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion.

The activation of heterodimeric (α/ß) integrin transmembrane receptors by cytosolic protein talin is crucial for regulating diverse cell-adhesion-dependent processes, including blood coagulation, tissue remodeling, and cancer metastasis. This process is triggered by the coincident binding of N-terminal FERM (four-point-one-protein/ezrin/radixin/moesin) domain of talin (talin-FERM) to the inner membrane surface and integrin ß cytoplasmic tail, but how these binding events are spatiotemporally regulated remains obscure. Here we report the crystal structure of a dormant talin, revealing how a C-terminal talin rod segment (talin-RS) self-masks a key integrin-binding site on talin-FERM via a large interface. Unexpectedly, the structure also reveals a distinct negatively charged surface on talin-RS that electrostatically hinders the talin-FERM binding to the membrane. Such a dual inhibitory topology for talin is consistent with the biochemical and functional data, but differs significantly from a previous model. We show that upon enrichment with phosphotidylinositol-4,5-bisphosphate (PIP2) - a known talin activator, membrane strongly attracts a positively charged surface on talin-FERM and simultaneously repels the negatively charged surface on talin-RS. Such an electrostatic "pull-push" process promotes the relief of the dual inhibition of talin-FERM, which differs from the classic "steric clash" model for conventional PIP2-induced FERM domain activation. These data therefore unravel a new type of membrane-dependent FERM domain regulation and illustrate how it mediates the talin on/off switches to regulate integrin transmembrane signaling and cell adhesion.

Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation.

Kindlin-2 belongs to an emerging class of regulators for heterodimeric (α/ß) integrin adhesion receptors. By binding to integrin ß cytoplasmic tail via its C-terminal FERM-like domain, kindlin-2 promotes integrin activation. Intriguingly, this activation process depends on the N terminus of kindlin-2 (K2-N) that precedes the FERM domain. The molecular function of K2-N is unclear. We present the solution structure of K2-N, which displays a ubiquitin fold similar to that observed in kindlin-1. Using chemical shift mapping and mutagenesis, we found that K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate. We show that while wild-type kindlin-2 is capable of promoting integrin activation, such ability is significantly reduced for its membrane-binding defective mutant. These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation.

Case report--death by subcutaneous injection of cyanide in Sri Lanka.

An elderly man was stabbed with a needle and syringe onto his abdomen while asleep. He progressively developed respiratory failure and coma and died an hour later. Autopsy findings and laboratory analysis confirmed the death as being due to poisoning by cyanide. This case highlights the need to consider cyanide as a possible agent where there is a rapid death with progressive respiratory failure after injection of an unknown substance. Cyanide poisoning by ingestion is frequently seen in suicidal, accidental and homicidal deaths. To our knowledge, this is the first reported case of cyanide poisoning by injection in Sri Lanka.

Mental health status and risk factors for mental health problems in left-behind children of women migrant workers in Sri Lanka.

INTRODUCTION: Many married Sri Lankan women annually migrate for employment overseas. Despite widely speculated psychological consequences in these children, their mental health status has not been systematically studied using validated instruments. OBJECTIVES: To describe mental health status of children of women overseas workers and compare that with children of locally employed women, and to describe socio-demographic factors and risk factors associated with abnormal mental health in these children. METHODS: A cross sectional comparative survey was conducted among 253 children (aged 5-10 years) of women migrant workers in the Colombo District and age and sex matched controls from same neighbourhood. Tools used were the validated Sinhala translation of Child Behaviour Check List (CBCL-S) and questionnaires on socio-demographic/risk factors and school functioning. RESULTS: Mean CBCL-S scores and proportion of children with mental health problems were significantly higher in the study group. Not having an elder sibling, father not living with child, mother educated up to grade 5 or less, change of principal carer (PC) twice or more, living with a relative (or not living in own home), child not communicating freely with PC, and not being permitted to engage in recreational activities at school were significantly associated with abnormal mental health of children of migrant women. CONCLUSIONS: A high awareness is required among health and social care authorities regarding mental health problems in these children and relevant risk factors in order to take preventive measures.

Prevalence of attention deficit hyperactivity disorder (ADHD) in children presenting with self-inserted nasal and aural foreign bodies.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the commonest behaviour disorders in children, characterized by hyperactivity, inattention and impulsiveness. Tendency towards risk-taking behaviour and accident proneness is well recognized in these children. Accordingly, it could be hypothesized that children with ADHD are at increased risk for self-inserting foreign bodies, but a Medline search did not reveal any studies that investigated this possibility. OBJECTIVES: To study the prevalence of ADHD among children seen with self-inserted foreign bodies. METHOD: Children attending ENT service in a tertiary care children's hospital with self-inserted foreign bodies were assessed for the presence of ADHD. Two rating scales, Strengths and Difficulties Questionnaire (SDQ)-Parent Version, and Conners Parent Rating Scale (CPRS) were used to identify the cardinal features of ADHD. RESULTS: A total of 34 children, age 3-10 years, participated in the study. Majority (51.6%) were female. Nearly 25% had one or more previous incidents of foreign body insertion and 20% had previous accidental injuries that needed hospitalization. A prevalence of 14.3% for ADHD was identified, which is almost 3 times more than that reported in a previous study among children attending medical and surgical outpatient clinics (5.1%). High rates for abnormal hyperactivity scores were reported by parents, 37.4% with SDQ and 20% with CPRS. Although 64.7% of the sample was under 5 years, almost all children who were identified with ADHD belonged to 5-10 year age group, thus effectively excluding younger aged children who may have age related apparent hyperactivity. CONCLUSIONS: Awareness of possible association between self-insertion of foreign bodies and ADHD is needed and an assessment for hyperactivity/ADHD is justified in such children, especially in those over the age of 5 years.

Screening of 18-24-month-old children for autism in a semi-urban community in Sri Lanka.

All children aged 18-24 months in a defined geographical area were initially screened for autism, using 'Red Flag' criteria. All the children with one or more positive 'Red Flag' signs were further screened using Modified Checklist for Autism in Toddlers (M-CHAT) translated to Sinhala, followed by a comprehensive clinical assessment. Of a sample of 374 children, 'Red Flag' signs were positive in 28 (7.4%). Four children received a diagnosis of autism on clinical assessment giving a prevalence of 1.07% or 1 per 93 in the 18-24-month age group. Sensitivity of M-CHAT was only 25%, and specificity 70%. The high prevalence detected strongly justifies early community-based screening, but a culturally sensitive screening tool needs to be developed for Sri Lanka.