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An 89-year-old woman with a history of hypertension and hypothyroidism was referred to the cardiology clinic because of progressively worsening shortness of breath. She managed all daily activities independently. Her symptoms had been present for several years, with notable deterioration over the past few months. Recently, she had been evaluated in the emergency department for acute dyspnoea and treated for an upper respiratory tract infection, but her symptoms persisted. A review of her medical history revealed significant indicators. In 2009, she had palpitations and dizziness, which were attributed to postural hypotension, prompting adjustments in her antihypertensive regimen. In 2013, she was treated for bilateral carpal tunnel syndrome. In 2019, her NT-proBNP level was elevated at 547 ng/L, and echocardiography showed moderate left ventricular hypertrophy (LVH). She was diagnosed with hypertensive heart disease and had her medications adjusted. Despite a history of smoking, no significant chronic obstructive pulmonary disease (COPD) was found to explain her persistent shortness of breath. In April 2024, she was again admitted for acute dyspnoea and treated for an upper respiratory infection. Although she showed some improvement, her symptoms did not resolve entirely. By May 2024, her GP referred her back to cardiology because her dyspnoea remained unchanged, and she developed bilateral ankle oedema. During this visit, her shortness of breath was classified as New York Heart Association (NYHA) Class III. Examination revealed congestion, raised jugular venous pressure (JVP) and peripheral oedema. NT-proBNP increased to 1204 ng/L, and cardiac troponin was mildly elevated at 28 ng/L. Electrocardiography (ECG) demonstrated a pseudo-infarct pattern (Fig 1). Repeat echocardiography revealed severe LVH with a restrictive filling pattern, raising suspicion of an infiltrative cardiomyopathy, such as cardiac amyloidosis. Further investigations, including serum and urine immune electrophoresis and free light chain analysis, were negative. Given the high clinical suspicion, she was referred to the National Amyloidosis Center, where a 99mTc-DPD bone scan revealed Grade III radiotracer uptake, confirming the diagnosis of transthyretin (TTR) cardiac amyloidosis. She started tafamidis, a TTR stabiliser, leading to marked improvement in her symptoms and overall quality of life. This case underscores the importance of recognising cardiac amyloidosis, often overlooked in clinical practice. Patients usually experience diagnostic delays of 4 to 5 years, resulting in missed opportunities for early intervention.1 A high index of suspicion is essential, particularly in older patients with unexplained heart failure symptoms, progressive LVH and autonomic dysfunction.2 This patient's red flags (longstanding dyspnoea despite controlled hypertension, a history of bilateral carpal tunnel syndrome, rising NT-proBNP levels and hypotension) could have facilitated an earlier diagnosis. Enhanced clinical awareness and a comprehensive approach to unexplained heart failure symptoms are crucial, because early recognition and treatment can significantly improve patient outcomes.3

The purpose of this study is to examine the relationship between renewable energy sources and sustainable economic growth of the South Asian Association for Regional Cooperation (SAARC) countries. This study uses three main renewable energy sources such as geothermal, hydro and wind. This study collects dataset from SAARC countries from 1995 to 2018. This study applies a fixed-effect test and panel vector error correction model (PVECM) test for data analysis. The overall results show that all three renewable energy sources have positively significant impacts on economic development among SAARC countries’ economies. Moreover, the hydropower renewable energy source has more effects and influences on economic growth as relatively compared with the rest of the two individual sources of renewable energy.

Decoration of phytochemicals contributes to the majority of metabolic diversity in nature, whereas how this process alters the biological functions of their precursor molecules remains to be investigated. Flavones, an important yet overlooked subclass of flavonoids, are most commonly conjugated with sugar moieties by UDP-dependent glycosyltransferases (UGTs). Here, we report that the natural variation of rice flavones is mainly determined by OsUGT706D1 (flavone 7- O -glucosyltransferase) and OsUGT707A2 (flavone 5- O -glucosyltransferase). UV-B exposure and transgenic evaluation demonstrate that their allelic variation contributes to UV-B tolerance in nature. Biochemical characterization of over 40 flavonoid UGTs reveals their differential evolution in angiosperms. These combined data provide biochemical insight and genetic regulation into flavone biosynthesis and additionally suggest that adoption of the positive alleles of these genes into breeding programs will likely represent a potential strategy aimed at producing stress-tolerant plants. In contrast to flavonols, the functions of plant flavones are largely unknown. Here, the authors report the two differentially evolved glucosyltranferases (flavone 7- O -glucosyltransferase and flavone 5- O -glucosyltransferase) determine natural variation of rice flavone accumulation and UV-tolerance.

Background Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation. Methods In this study, healthy adult male rabbits of local strain were divided into 4 groups ( n  = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups. Results Significantly ( p  < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40–60% increased oxidative stress compared to control, in a dose-dependent manner. Conclusions These results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.

Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates. We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression. 153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance. Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.

Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age [greater than or equal to] 35-40 weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates. We conducted a single-center quasi-experimental study for this quality improvement project using PCC among the preterm neonates admitted in a tertiary care level-III NICU at the Aga Khan University Hospital Karachi, Pakistan, received caffeine therapy, and survived at discharge. The researchers compared pre-PCC data (April-December 2017) with post-PCC data (April-Dec 2018) each for nine months, with three months intervals (January-March 2018) of PCC formulation and implementation phase. The study was conducted according to the SQUIRE2.0 guidelines. The Data were collated on factors influencing MA, including the cost of therapy, medication refill rates, and parental complaints as primary outcome measures. The Risk factors of HRA were included as secondary outcomes. After PCC implementation cost of therapy was reduced significantly from Rs. 97000.0 (729.0 USD) to Rs. 24500.0 (185.0 USD) (p<0.001), significantly higher (p<0.001) number of patients completed remaining refills (77.6% pre-phase vs 97.5% post-phase). The number of parental complaints about cost, ampoule usage, medication drawing issue, wastage, inappropriate dosage form, and longer duration of therapy reduced significantly in post-phase. HRA reduced from 25% to 6.6% (p<0.001). Post-implementation of PCC (RR 0.14; 95% CI: 0.07-0.27) was a significant independent risk factor for reducing HRA using a multivariate analysis model. Longer duration of caffeine therapy after discharge (RR 1.05; 95% CI: 1.04-1.04), those who were born in multiple births (RR 1.15; 95% CI: 1.15-1.15), and those who had higher number of siblings were other significant independent risk factors for HRA. PCC dispensation in the appropriate dosage form at discharge effectively reduced cost, non-adherence to therapy, and risk of hospital readmissions. This neonatal clinical and compounding pharmacist-led model can be replicated in other resource-limiting setting.

Key messageSecond generationBt insecticidal toxin in comibination withAllium sativumleaf agglutinin gene has been successfully expressed in cotton to develop sustainable resistance against major chewing and sucking insects. The first evidence of using the Second-generation Btgene in combination withAllium sativum plant lectin to develop sustainable resistance against chewing and sucking insects has been successfully addressed in the current study.Excessive use of Bt δ-endotoxins in the field is delimiting its insecticidal potential. Second-generation Bt Vip3Aa could be the possible alternative because it does not share midgut receptor sites with any known cry proteins. Insecticidal potential of plant lectins against whitefly remains to be evaluated. In this study, codon-optimized synthetic Bt Vip3Aa gene under CaMV35S promoter and Allium sativum leaf agglutinin gene under phloem-specific promoter were transformed in a local cotton variety. Initial screening of putative transgenic cotton plants was done through amplification, histochemical staining and immunostrip assay. The mRNA expression of Vip3Aa gene was increased to be ninefold in transgenic cotton line L6P3 than non-transgenic control while ASAL expression was found to be fivefold higher in transgenic line L34P2 as compared to non-transgenic control. The maximum Vip3Aa concentration was observed in transgenic line L6P3. Two copy numbers in homozygous form at chromosome number 9 and one copy number in hemizygous form at chromosome number 10 was observed in transgenic line L6P3 through fluorescent in situ hybridization. Significant variation was observed in transgenic cotton lines for morphological characteristics, whereas physiological parameters of plants and fiber characteristics (as assessed by scanning electron microscopic) remained comparable in transgenic and non-transgenic cotton lines. Leaf-detach bioassay showed that all the transgenic lines were significantly resistant to Helicoverpa armigera showing mortality rates between 78% and 100%. Similarly, up to 95% mortality of whiteflies was observed in transgenic cotton lines when compared with non-transgenic control lines.

Purpose of ReviewMultiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment.Recent FindingsIn contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD.SummaryWe review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.

ObjectiveNutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit (NICU) and evaluated their outcomes.DesignThis was a quality improvement initiative. Data were collected retrospectively before and after the intervention.SettingA tertiary-care level 3 NICU at the Aga Khan University in Karachi, Pakistan.PatientsAll NICU patients who received individualised PN (IPN) from December 2016 to August 2017 and SPN from October 2017 to June 2018.InterventionsA team of neonatologists and nutrition pharmacists collaborated to design two evidence-based SPN solutions for preterm neonates admitted to the NICU.Main outcome measuresWe recorded mean weight gain velocity from days 7 to 14 of life. The other outcomes were change in weight expressed as z-scores, metabolic abnormalities, PN-associated liver disease (PNALD), length of NICU stay and episodes of sepsis during hospital stay.ResultsNeonates on SPN had greater rate of change in weight compared with IPN (β=13.40, 95% CI: 12.02 to 14.79) and a smaller decrease in z-scores (p<0.001). Neonates in the SPN group had fewer hyperglycemic episodes (IPN: 37.5%, SPN: 6.2%) (p<0.001), electrolyte abnormalities (IPN: 56.3%, SPN: 21%) (p<0.001), PNALD (IPN: 52.5%, SPN: 18.5%) (p<0.001) and sepsis (IPN: 26%, SPN: 20%) (p<0.05). The median length of stay in NICU was 14.0 (IQR 12.0–21.0) for the IPN and 8.0 (IQR 5.0–13.0) days for the SPN group.ConclusionsWe found that SPN was associated with shorter NICU stay and greater weight gain. In-house preparation of SPN can be used to address the nutritional needs in resource-limited settings where commercially prepared SPN is not available.

Background Parenteral nutrition (PN) preparations are listed as high-alert medications and have a high probability of medication errors (MEs). Board-certified Nutrition Support Pharmacists (BCNSPs) can play an important role in reducing PN-associated complications by highlighting the gaps in the PN prescribing process. This study aimed to determine the impact of BCNSP-led PN review on the identification and documentation of prescribing MEs (PMEs) to optimize quality and safety in PN prescribing processes. Methods This QI quasi-experimental study included all neonates admitted to a level III neonatal intensive care unit (NICU) and prescribed PN. All identified and recognized PN-PMEs documented by pharmacists were evaluated in pre-and post-implementation-phases. In the pre-phase, the PN-duty pharmacist reviewed all the neonatal PN-orders while located in the pharmacy, and in the post-phase, a clinically involved BCNSP performed this task. All PN-PMEs were categorized into ten types. Predictors of PN-PMEs were analyzed through logistic regression. Results PN-orders were prescribed to 98 and 112 neonates in pre-and post-phases, respectively. For demographic and clinical variables, neonates were comparable. A median of 12 (range = 9 − 19) vs. 15 (range = 12–22) PN-orders/day were reviewed in pre-and post-phases. Documented PN-PMEs for all PN orders were significantly higher in the post-phase (212/2577, 8.23%) compared with the pre-phase (25/2577, 0.97%; p  < 0.001). “Wrong Dose/Calculation” was the most reported category (88/2577, 3.41%). “Wrong concentration range” was the second highest (29/1309, 2.22%) and all were reported only in post-phase. Additional errors involved infusion, compatibility, and osmolarity deviations, renal/hepatic dose adjustment errors and stability errors. Most of them were only identified in the post-phase. Post-phase outcomes showed clinically meaningful reductions in metabolic derangements, NICU stay, and mortality ( p  < 0.001). Conclusion The engagement of BCNSPs in the clinical neonatal setting for PN management may improve the safety and efficacy of PN-therapy.