Remarkably Selective Binding, Behavior Modification, and Switchable Release of (Bipyridine)3Ru(II) vis-à-vis (Phenanthroline)3Ru(II) by Trimeric Cyclophanes in Water.

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, the more valuable the dream becomes. We now present multianionic trimeric cyclophane receptors with a remarkable ability to bind the iconic (bipyridine)3Ru(II) (with its huge range of applications) while rejecting the nearly equally iconic (phenanthroline)3Ru(II). These receptors not only selectively capture (bipyridine)3Ru(II) but also can be redox-switched to release the guest. 1D- and 2D(ROESY)-NMR spectroscopy, luminescence spectroscopy, and molecular modeling enabled this discovery. This outcome allows the control of these applications, e.g., as a photocatalyst or as a luminescent sensor, by selectively hiding or exposing (bipyridine)3Ru(II). Overall, a 3D nanometric object is selected, picked-up, and dropped-off by a discrete molecular host. The multianionic receptors protect excited states of these metal complexes from phenolate quenchers so that the initial step in photocatalytic phenolate oxidation is retarded by nearly 2 orders of magnitude. This work opens the way for (bipyridine)3Ru(II) to be manipulated in the presence of other functional nano-objects so that many of its applications can be commanded and controlled. We have a cyclophane-based toolkit that can emulate some aspects of proteins that selectively participate in cell signaling and metabolic pathways by changing shape upon environmental commands being received at a location remote from the active site.

Duplication errors due to brand name confusion; It is not always the name-Short case series.

Confusion of drug names has been identified as a leading cause of medication errors and potential iatrogenic harm. Most of these errors occur because of look-alike or sound-alike drugs. This case series gives examples of duplication errors due to brand confusion, where there are no similarities in the names.

Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests.

BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.

A Tool, an App and a Field: Fluorescent PET Sensors, Blood Electrolyte Analysis and Molecular Logic as Products of Supramolecular Photoscience from Northern Ireland and Sri Lanka.

The general tool of fluorescent PET (photoinduced electron transfer) sensors/switches - a molecular design principle with engineering features - is outlined, with the aid of frontier orbital energy diagrams. Fluorophores such as anthracene, 1,3-diaryl-Δ2 -pyrazolines and 4-amino-1,8-naphthalimides are employed within this system, alongside receptors such as amines, carboxylates, crown ethers and amino acids. This tool appealed to a multinational corporation for building a medical analyzer for electrolytes such as Na+ , K+ , Ca2+ and gases like CO2 , which became a commercially successful application. Finally, the tool was a springboard for chemistry to cross into computer science. The field of molecular logic can elucidate how molecules inside us handle information. Molecular examples of the simplest logic gates such as YES, NOT, OR, AND are described. A case of a human-level computation - visual edge detection - is also included.

Multiple molecular logic gate arrays in one system of (2-(2'-pyridyl)imidazole)Ru(ii) complexes and trimeric cyclophanes in water.

Shape-switchable cyclophane hosts allow the controlled capture and release of reactive polypyridineRu(ii) complexes in water. This gives rise to a network of host-guest binding, acid-base reactions in ground and excited states, and chemical redox interconversions. In the case of (2-(2'-pyridyl)imidazole)Ru(ii) complexes, several molecular logic gate arrays of varying complexity emerge as a result. Cyclophane-induced 'off-on' switching of luminescence in neutral solution is found to originate from two features of these aromatic hosts: enhancement of radiative decay by the polarizable host and the suppression of nonradiative decay involving deprotonation by reducing the water content within the deep host cavity. These are examples of nanometric coordination chemistry/physics being controlled by inclusion in an open box. The aromatic units of the macrocycle are also responsible for the shape-switching mechanism of wall collapse/erection.

Recurrent vaginal vault dehiscence and evisceration following total laparoscopic hysterectomy, successfully repaired with polypropylene mesh and sacrocolpopexy.

Recurrent vault dehiscence is a rare and potentially serious complication following hysterectomy. We report a rare case of recurrent vault dehiscence and evisceration following a total laparoscopic hysterectomy (TLH) which was successfully repaired with polypropylene mesh and sacro-colpopexy. A 47-year-old multiparous woman underwent TLH for adenomyosis. During the surgery, vaginal wall was incised with monopolar diathermy and sutured with synthetic absorbable barbed suture in a single layer. She presented 12 weeks later with vault dehiscence and evisceration of omentum. Laparoscopically, eviscerated omental part was removed and the vaginal cuff was repaired vaginally with absorbable synthetic suture. She came with a recurrence in 3 months with vault dehiscence and a vault prolapse without any evisceration. She underwent laparoscopic mesh repair of the vault combined with laparoscopic Sacro-colpopexy with complete recovery. Incidence of vault dehiscence is found to be higher in TLH than abdominal or vaginal hysterectomy. Treatment options for recurrent vault dehiscence involve strengthening the vault with tissues, or with a prosthesis.

Counting on U training to enhance trusting relationships and mental health literacy among business advisors: protocol for a randomised controlled trial.

BACKGROUND: Financial distress is thought to be a key reason why small-medium enterprise (SME) owners experience higher levels of mental health conditions compared with the broader population. Business advisors who form trusting, high-quality relationships with their SME clients, are therefore well placed to: (1) help prevent/reduce key sources of financial distress, (2) better understand the business and personal needs of their clients and, (3) recognise the signs and symptoms of mental health conditions and encourage help-seeking where appropriate. The aim of this study is to compare the effectiveness of relationship building training (RBT) combined with mental health first aid (MHFA) training for business advisors with MHFA alone, on the financial and mental health of their SME-owner clients. METHODS: This is a single blind, two-arm randomised controlled trial. Participants will be business advisors who provide information, guidance and/or assistance to SME owner clients and are in contact with them at least 3 times a year. The business advisors will invite their SME-owner clients to complete 3 online surveys at baseline, 6- and 12-months. Business advisors will be randomised to one of two conditions, using a 1:1 allocation ratio: (1) MHFA with RBT; or (2) MHFA alone, and complete 3 online surveys at baseline, 2- and 6-months. Primary outcomes will be measured in the business advisors and consist of the quality of the relationship, stigmatizing attitude, confidence to offer mental health first aid, quality of life and provision of mental health first aid. Secondary outcomes will be measured in the SME owners and includes trust in their business advisors, the quality of this relationship, financial wellbeing, financial distress, psychological distress, help-seeking behaviour, and quality of life. To complement the quantitative data, we will include a qualitative process evaluation to examine what contextual factors impacted the reach, effectiveness, adoption, implementation, and maintenance of the training. DISCUSSION: As there is evidence for the connections between client trust, quality of relationship and financial and mental wellbeing, we hypothesise that the combined RBT and MHFA training will lead to greater improvements in these outcomes in SME owners compared with MHFA alone. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04982094 . Retrospectively registered 29/07/2021. The study started in February 2021 and the recruitment is ongoing.

Direct and indirect costs for hospitalized patients with dengue in Southern Sri Lanka.

BACKGROUND: The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system. METHODS: From June 2017-December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars. RESULTS: A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%. CONCLUSIONS: Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.

Taming Tris(bipyridine)ruthenium(II) and Its Reactions in Water by Capture/Release with Shape-Switchable Symmetry-Matched Cyclophanes.

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These reactions of an iconic class of molecules─polypyridineRu(II)─are now controlled by capturing or releasing three of them with hosts that are shape-switchable. Reversible erection or collapse of the host walls allows such switchability. Some reaction rates are suppressed by factors of up to 120 by inclusive binding of the metal complexes. This puts nanometric coordination chemistry in a box that can be open or shut as necessary. Such second-sphere complexation can allow considerable control to be exerted on photocatalysis, electrocatalysis, and luminescent sensing involving polypyridineRu(II) compounds. The capturing states of hosts are symmetry-matched to guests for selective binding and display submicromolar affinities. A perching complex, which is an intermediate state between capturing and releasing states, is also demonstrated.

Opportunities to prevent and manage undernutrition to amplify efforts to end TB.

The bidirectional relationship between TB and nutrition is well recognized - primary undernutrition is a risk factor for developing TB disease, while TB results in wasting. Although nutrition support is acknowledged as an important intervention in TB programmes, it is seldom afforded commensurate priority for action. TB incidence and deaths worldwide are falling too slowly to meet WHO End TB Strategy milestones, and the number of undernourished people is increasing, likely to be further exacerbated by the ongoing COVID-19 pandemic. Undernutrition needs to be more urgently and intensively addressed. This is especially true for the WHO South-East Asia Region, where the high rates of undernutrition are a key driver of the TB epidemic. The evidence base has been sufficiently robust for clear and workable programmatic guidance to be formulated on assessment, counselling and interventions for TB patients. Many high-burden countries have developed policies addressing TB and nutrition. Gaps in research to date have frustrated the development of more refined programmatic approaches related to addressing TB and malnutrition. Future research can be shaped to inform targeted, actionable policies and programmes delivering dual benefits in terms of undernutrition and TB. There are clear opportunities for policy-makers to amplify efforts to end TB by addressing undernutrition.

Comparison of two rapid test kits with real time polymerase chain reaction for early diagnosis of dengue in Sri Lanka.

Dengue is among the deadliest insect-borne diseases circulating in Sri Lanka. Most of the infections that are diagnosed early are manageable. However, delays in diagnosis may cause fatalities. We evaluated the dengue NS1 antigen card and NS1 SD kit for early diagnosis of dengue using samples from 116 RT-PCR-positive patients admitted within 5 days of the fever onset. RT-PCR tests were performed as standard tests. IgM and IgG ELISA tests were carried out to identify primary and secondary infections. Of the 116 patients who tested positive for dengue using PCR, 48 were positive using NS1 antigen card and 45 were positive using NS1 SD. Patients with 100 copies or higher viral load showed a higher sensitivity in both antigen card and NS1 SD. Of 34 primary infections evaluated, 23 were positive by NS1 antigen card, while the positivity was 21 by NS1 SD. Of the 30 secondary infections evaluated, 15 were positive by NS1 antigen card while 14 by NS1 SD. Our findings showed that while the rapid tests are convenient and much easier to use than PCR, they are less sensitive and need improvement. Until then, clinical diagnosis should have more emphasis on the early diagnosis of dengue.

A Range-Based Algorithm for Autonomous Navigation of an Aerial Drone to Approach and Follow a Herd of Cattle.

This paper proposes an algorithm that will allow an autonomous aerial drone to approach and follow a steady or moving herd of cattle using only range measurements. The algorithm is also insensitive to the complexity of the herd's movement and the measurement noise. Once arrived at the herd of cattle, the aerial drone can follow it to a desired destination. The primary motivation for the development of this algorithm is to use simple, inexpensive and robust sensing hence range sensors. The algorithm does not depend on the accuracy of the range measurements, rather the rate of change of range measurements. The proposed method is based on sliding mode control which provides robustness. A mathematical analysis, simulations and experimental results with a real aerial drone are presented to demonstrate the effectiveness of the proposed method.

Genotypic variation of the interactive effects of elevated temperature and CO2 on leaf gas exchange and early growth of sugarcane.

Increased atmospheric CO2 and consequent increases in temperature are two prominent features of climate change, a major challenge to crops. Here, our objectives were to determine: (1) the responses of sugarcane during the first 90 days of elevated CO2 (ECO2 ) and elevated temperature (ETem), both individually and together, and (2) the genotypic variation of these responses. Eight varieties were grown both in open-top chambers in a factorial combination of ambient/ECO2 concentrations (344-351/777-779 ppm) and ambient/ETem (34.9-35.6/36.6-38.4°C) and in open fields. Significant treatment × variety interaction effects were observed on leaf net photosynthetic rate (An ), stomatal conductance (gs ), transpiration rate (El ), and instantaneous transpiration efficiency (TE ). In most varieties, ECO2 alone did not affect An, but the combination of ECO2 and ETem decreased An . ECO2 decreased gs and El while increasing TE in all varieties. These effects were amplified when ETem was combined with ECO2 . ETem alone had variable effects on An and gs depending on variety, while it increased El and did not affect TE in a majority of varieties. Germination, tillering and stem diameter were not affected by treatments and did not show varietal variation. Leaf water potential, chlorophyll (spad), leaf area, and aboveground dry weight per plant showed varietal variations but were not affected by treatments. The variable responses to ETem and the significant genotypic variation to ECO2 and elevated temperature (ETem) observed in this work, both individually and together, demonstrate a considerable scope to breed sugarcane varieties for a future high-CO2 and warmer climate.

Symptomatology and Serum Nuclear Magnetic Resonance Metabolomics; Do They Predict Endometriosis in Fertile Women Undergoing Laparoscopic Sterilisation? A Prospective Cross-sectional Study.

Endometriosis is a common, chronic inflammatory condition, thought to have a higher incidence in symptomatic women, yet, commonly associated symptoms do not always correlate with the presence or severity of disease and diagnosis requires surgery. We prospectively collected data and assessed symptomology and NMR spectroscopy-based metabolomics of 102 women undergoing laparoscopic sterilisation at a tertiary referral centre in a cross-sectional study. Twelve women were incidentally diagnosed with endometriosis (11.7%). According to the pre-operative questionnaire, presence and absence of many symptoms usually attributed to endometriosis were declared at similar frequencies in women with or without endometriosis. Women with endometriosis reported apparently more persistent heavy periods (50% vs 18.9%), prolonged periods (25% versus 7.8%) and problems conceiving (27.3% versus 9%) than those without endometriosis. NMR could not discern any distinguishable differences in the serum metabolome between those with and without endometriosis. Our paper highlights the complex symptomology experienced by women, regardless of a surgical diagnosis of endometriosis. Previous literature and the current study failed to identify clear, distinguishable symptoms or biomarkers pertinent to surgically confirmed endometriosis in the general population. Therefore, development of effective, non-invasive tests for identifying this heterogenous benign condition, endometriosis, is likely to be challenging.

Fluorescent Molecular Logic Gates Driven by Temperature and by Protons in Solution and on Solid.

Temperature-driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5-trisubstituted Δ2 -pyrazoline on its own and when grafted onto silica microparticles. Related Δ2 -pyrazolines become proton-driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small-molecule systems, a polymeric molecular thermometer based on a benzofurazan-derivatized N-isopropylacrylamide copolymer is attached to silica to produce temperature-driven fluorescent YES logic.

Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka.

A significant decrease in dengue fever cases and a contrasting increase in leptospirosis cases were reported for the second quarter of 2020 compared with 2019 in Sri Lanka. In the absence of significant environmental and weather-related differences to account for these changes in incidence, we investigated the possibility that the effects of the COVID-19 pandemic on public health, social behaviour and the restrictions imposed during the lockdown influenced the fluctuations in dengue and leptospirosis infections.

A Colorimetric Method for Quantifying Cis and Trans Alkenes Using an Indicator Displacement Assay.

A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using 96-well plates two steps are performed: a reaction plate for dihydroxylation of the alkenes followed by an IDA screening plate consisting of an indicator and a boronic acid. The dihydroxylation generates either erythro or threo vicinal diols from cis or trans alkenes, depending upon their syn- or anti-addition mechanisms. Threo diols preferentially associate with the boronic acid due to the creation of more stable boronate esters, thus displacing the indicator to a greater extent. The generality of the protocol was demonstrated using seven sets of cis and trans alkenes. Blind mixtures of cis and trans alkenes were made, resulting in an average error of ±2 % in the percentage of cis or trans alkenes, and implementing E2 and Wittig reactions gave errors of ±3 %. Furthermore, we developed variants of the IDA for which the color may be tuned to optimize the response for the human eye.

Changing phenotype, early clinical course and clinical predictors of inflammatory bowel disease in Sri Lanka: a retrospective, tertiary care-based, multi-centre study.

BACKGROUND: Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. METHODS: We included patients [diagnosed between June/2003-December/2009-Group-1(G1), January/2010-June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration < 3-years) and CP of poor outcomes (disease duration ≥ 1-year) was assessed. Poor outcomes were complicated-disease (CompD-stricturing/penetrating-CD, extensive-UC/pancolitis, perforation/bleeding/colectomy/malignancy) and treatment-refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory and biologic use). RESULTS: 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p < 0.01). Increase of CD from G1-to-G2 was significant (23-45.4%, p < 0.001). In both groups, left-sided colitis (E2) and ileo-colonic (L3)/non-stricturing, non-penetrating disease behaviour (B1) CD predominated. Extensive-colitis (E3) (36.4% vs 22.7, p < 0.05) and stricturing-CD (B2) (26.1% vs 4.0%, p < 0.01) was commoner in G1. ECC was assessed in 173-patients (UC-94, CD-79). Aggressive disease behaviour and TRD were low among both UC and CD. Immunomodulator use was significantly higher among CD than UC (61.5% vs 29.0% respectively, p < 0.01). Anti-TNF use was low among both groups (UC-3.2%, CD-7.7%). Disease complications among UC [bleeding (2.1%), malignancy-(1.1%), surgery-(2.1%)] and CD [stricture-(3.9%), perforation-(1.3%), malignancy-(1.3%), surgery-(8.9%)] were generally low. CPs were assessed in 271-patients (UC-163, CD-108). Having a family history of IBD (for UC), extraintestinal manifestation (EIM), severe disease at presentation, being in younger age categories and severe disease at presentation, (for both UC and CD) predicted poor outcomes. CONCLUSION: There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes.