Demystifying non-invasive approaches for screening jaundice in low resource settings: a review.

All national and international pediatric guidelines universally prescribe meticulous bilirubin screening for neonates as a critical measure to mitigate the incidence of acute bilirubin encephalopathy (ABE) and Kernicterus. The prevailing gold standard for jaundice detection in neonates necessitates invasive blood collection, followed by subsequent biochemical testing. While the invasive procedure provides dependable bilirubin measurements and continues to be the sole gold standard diagnostic method for assessing bilirubin concentration. There exists a pressing need to innovate non-invasive screening tools that alleviate the sampling stress endured by newborns, mitigate iatrogenic anemia, and expedite the turnaround time for obtaining results. The exploration of non-invasive modalities for bilirubin measurements is gaining momentum, driven by the overarching goal of minimizing the number of pricks inflicted upon neonates, thereby rendering screening a swift, efficient, comfortable, and dependable process. This comprehensive review article delves extensively into the array of non-invasive approaches and digital solutions that have been proposed, implemented, and utilized for neonatal bilirubin screening, with a particular emphasis on their application in low-resource settings. Within this context, the review sheds light on the existing methodologies and their practical applications, with a specific focus on transcutaneous bilirubin meters. Moreover, it underscores the prevailing open challenges in this domain and outlines potential directions for future research endeavors. Notably, the review underscores the imperative need for robust educational programs targeted at both families and healthcare personnel to expedite the process of seeking timely care for neonatal jaundice. Additionally, it underscores the necessity for the development of enhanced screening and diagnostic tools that can offer greater accuracy in clinical practice.

Carbonized Tetracycline: a new class of nanomaterial with tuneable antioxidant, reduced cytotoxicity, immunomodulatory, and osteogenic properties.

Tetracycline (TET), a broad-spectrum antibiotic, also possesses different non-antibiotic activities such as inhibition of metalloproteinase (MMP), anti-inflammatory, antioxidant, high bone affinity, etc. However, the comparatively low efficacy of these non-antibiotic properties along with adverse effects such as hyperpigmentation, phototoxicity, long-term skeletal retention, etc. have not helped their broad utilization similar to their use as an antibiotic. In a unique attempt to improve the non-antibiotic properties while reducing the adverse effects, we converted the TET to nano-carbons through partial carbonization. After sorting out two water-dispersible C-TETs (C-TET HT - hydrothermal and C-TET HP - hot plate) based on their improved antioxidant activity, they have been characterized through a host of analytical techniques that showed distinct differences in morphology, size, shape, and surface functionality. Excitingly, the C-TET HT and C-TET HP have shown differential biological activity in a dosage and time-dependent manner in terms of cytotoxicity, immunomodulation, and osteogenic activity that was found to be associated with their carbonized parameters. Overall, the carbonized nano-drugs, C-TET HT and C-TET HP have presented substantial early promises on their non-antibiotic properties that could be further explored to develop into some effective therapeutics.

Detection of red cell alloantibody prior to overflow phenomenon in a case of warm AIHA secondary to Chronic Lymphocytic Leukemia and Myasthenia Gravis: A case report.

INTRODUCTION: Defects in the lymphoid system have been linked to immune dysregulation, which might explain why lymphoid neoplasms and immunological disorders tend to occur concurrently. Chronic Lymphocytic Leukemia (CLL), characterised by the accumulation of dysfunctional lymphocytes, is associated with autoimmune cytopenias such as autoimmune haemolytic anaemia (AIHA). Detection of underlying alloantibody in warm AIHA, is challenging for any transfusion medicine specialist. This report highlights the significance of overflow phenomenon in detection of alloantibody in a case of warm AIHA secondary to CLL and myasthenia gravis. CASE REPORT: A 56-year-old male with a history of myasthenia gravis and thymoma progressed to B-cell CLL presented with severe anaemia and thrombocytopenia leading to multiple red blood cell (RBC) transfusions in the last two months. Clinical profile and laboratory workup suggested features of AIHA, and subsequent immunohaematological workup hinted towards an impending overflow phenomenon due to differential reactivity pattern observed between serum and eluate with antibody screen/identification panel. The eluate was pan-reactive with an antibody screen/ identification panel, while the serum showed a discrete anti-C alloantibody pattern. A compatible and antigen-negative RBC unit was successfully transfused, followed by medical management. DISCUSSION: The overflow phenomenon in AIHA depends on antibody titre and its affinity for RBC antigens. In the index case, the impending 'overflow or spillover' of autoantibodies into the patient's serum allowed us to detect underlying alloantibody without performing allogeneic adsorption and transfuse antigen-negative and crossmatch compatible PRBC unit. CONCLUSION: This case emphasises the significance of understanding the overflow phenomenon in AIHA as it can guide a transfusion medicine specialist in the early detection and identification of underlying alloantibodies, which is crucial for appropriate transfusion management in AIHA. However, early presentation and timely workup, along with a high level of suspicion, is crucial to identify this phenomenon.

Elucidating the relationship between red fluorescence and structural dynamics of carbon dots dispersed in different solvents.

The mechanism of intrinsic fluorescence of carbon dots (CDs), the latest nanomaterial from the carbon family, was supposedly deciphered through multiple theories. However, the much sought-after persistent red emission of CDs as a foreseeable consequence of experiments remains elusive prompting the question of whether tuning of the red emission of CDs is a predictable outcome or a serendipitous coincidence. Herein, we tried to decode the same by exploring Alizarin Red S (ARS)-based red emitting CDs in different solvents with wisely chosen analytical tools. The findings are aptly supported by molecular dynamics studies through an experimental intuition-driven model-building approach. Parallel interception of the CDs with powder X-ray diffraction (pXRD) and photophysical spectroscopic studies revealed an important relationship between the solvent and CDs. Tautomerism, a well-known phenomenon with chemical entities, was found to be operative for CDs that greatly influence the Stokes shift and ultimately the fluorescence outcome. Most importantly, pXRD studies established the turbostratism of the CDs where the well-ordered graphitic structure of CDs gets disrupted with solvent molecules. The extent of such disruption is a function of solvent and CD composition that plays a formidable role in obtaining red fluorescence. Thus, for the first time, we demonstrate that the red emission of CDs is related to its structural integrity and if taken care of could be sustained, a tremendously desirable outcome for relevant applications.

Effect of platelet-rich plasma on healing of autologous graft after anterior cruciate ligament reconstruction: a randomized control trial.

Aim: This study aimed to assess the effect of platelet-rich plasma (PRP) on anterior cruciate ligament (ACL) graft healing at graft tunnel interface and ACL graft 6 months post-reconstruction. Material & methods: A randomized trial involving 87 patients was conducted, dividing them into PRP and non-PRP groups. Magnetic resonance imaging (MRI) and functional outcome measures were used to evaluate graft healing. Results: Out of the 87 patients, 80 were analyzed. The PRP group exhibited superior clinical and radiological outcomes compared with the non-PRP group, as indicated by Figueroas score, Lysholm score and knee range of motion. Conclusion: These findings demonstrate that PRP can be used as an adjunct therapy for ACL reconstruction, enhancing graft healing and improving patient outcomes. CTRI approval (Reg. No - CTRI/2018/11/016263).

This study investigated the effects of platelet-rich plasma (PRP) on the healing of the anterior cruciate ligament (ACL) after knee reconstruction surgery. The ACL is an important ligament for knee stability, and its tear is a common sports injury. PRP, a substance found in blood, has been used to speed up healing in various surgeries. In this study, 80 patients who underwent ACL reconstruction were randomly assigned to receive either PRP or standard treatment. After 6 months, the group treated with PRP showed improved healing and better knee function compared with the non-PRP group. These findings suggest that PRP can help accelerate ACL healing and improve outcomes for patients.

Beneficial Intrinsic Hole Trapping and Its Amplitude Variation in a Highly Photoluminescent Toxic-Metal-Free Quantum Dot.

Intrinsic hole trapping as well as hole detrapping have not been observed for any quantum dot (QD) or perovskite nanocrystal (PNC) system. Moreover, amplitude variation of intrinsic hole trapping (or detrapping) has not been reported at all for any QD or PNC system. However, for a CuInS2-based core/alloy-shell (CAS) QD system, (a) both intrinsic hole trapping and detrapping have been observed and (b) very significant amplitude variations of hole trapping (∼16 to ∼42%) and hole detrapping (∼44 to 23%) have been observed. Unlike detrimental electron trapping, hole trapping has been shown to be beneficial, having a direct correlation toward increasing PLQY to 96%. Simultaneous electron and hole trapping has been shown to be quite beneficial for the CuInS2-based CAS QD system leading to the longest ON time (∼130 s) for which a nontoxic metal-based QD remains only in the ON-state without blinking.

The Effects of Language Barriers and Time Constraints on Online Learning Performance: An Eye-Tracking Study.

OBJECTIVE: The goal of this study is to model the effect of language use and time pressure on English as a first language (EFL) and English as a second language (ESL) students by measuring their eye movements in an on-screen, self-directed learning environment. BACKGROUND: Online learning is becoming integrated into learners' daily lives due to the flexibility in scheduling and location that it offers. However, in many cases, the online learners often have no interaction with one another or their instructors, making it difficult to determine how the learners are reading the materials and whether they are learning effectively. Furthermore, online learning may pose challenges to those who face language barriers or are under time pressure. METHOD: The effects of two factors, language use (EFL vs. ESL) and time constraints (high vs. low time pressure), were investigated during the presentation of online materials. The effects were analyzed based on eye movement measures (eye fixation rate-the total number of eye fixations divided by the task duration and gaze entropy) and behavioral measures (correct rate and task completion time). RESULTS: The results show that the ESL students had higher eye fixation rates and longer task completion times than the EFL students. Moreover, high time pressure resulted in high fixation rates, short task completion time, low correct rates, and high gaze entropy. CONCLUSION AND APPLICATION: The results suggest the possibility of using unobtrusive eye movement measures to develop ways to better assist those who struggle with learning in the online environment.

Redefining the role of therapeutic plasma exchange in complications of Echis carinatus sochureki envenomation refractory to anti-snake venom: A case series.

INTRODUCTION: Saw-scaled viper (Echis carinatus) belongs to the Viperidae family. Its venom is hemotoxic and contains several small peptides and proteins affecting the coagulation system. Commonly used anti-snake venom (ASV) products in India are reported to be ineffective or less effective in cases with bites by Echis carinatus sochureki which are commonly found in desert areas in Rajasthan. Although therapeutic plasma exchange (TPE) has been successful in patients with snakebite envenomation in the past, American Society for Apheresis guidelines 2019 included this indication under category III with grade 2C recommendation. AIM AND OBJECTIVES: To report the safety and efficacy of therapeutic plasma exchange procedures in the setting of ASV refractory E. c. sochureki envenomation. MATERIALS AND METHODS: Four patients admitted to our institute in 2021 September with an alleged history of snake bites and who underwent at least one cycle of therapeutic plasma exchange were assessed for clinical outcome, laboratory parameters, and blood product consumption. RESULTS: Three adult patients and one pediatric patient are included in this case series, all of them males. Indication for TPE in one case was suspected diffuse alveolar hemorrhage (DAH), while in all the other cases was thrombotic microangiopathy (TMA). All received a variable number of sessions from 2 to 5 and 1.3-1.5 plasma volume was removed on an average per cycle. The endpoint of TPE was the resolution of DAH in one while a reduction in lactate dehydrogenase and an increase in platelet count was in TMA cases. Consumption of blood products was drastically reduced in all four patients after starting the procedure. All the adult patients fared well on follow-up while the child had developed acute cortical necrosis and was dialysis-dependent. It has been noted in the previous studies too that a subset of snakebite-induced TMA cases was getting converted to chronic kidney disease and becoming dialysis dependent in the long run. CONCLUSIONS: In regions where ASV treatment failure is very common, therapeutic plasma exchange is a safe and effective complementary treatment modality along with supportive care.

Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani.

We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.

Excitation-Energy-Dependent Photoluminescence Quantum Yield is Inherent to Optically Robust Core/Alloy-Shell Quantum Dots in a Vast Energy Landscape.

The importance of alloy-shelling in optically robust Core/Alloy-Shell (CAS) QDs has been described from structural and energetic aspects. Unlike fluorescent dyes, both Core/Shell (CS) and CAS QDs exhibit excitation-energy-dependent photoluminescence quantum yield (PLQY). For both CdSe and InP CAS QDs (with metal- and nonmetal-based alloy-shelling, respectively), with increasing excitation energy, (a) the ultrafast rise-time or relaxation-time to the band-edge increases and (b) the magnitude of the normalized bleach signal decreases. Ultrasensitive single-particle spectroscopic investigation results showed that with decreasing excitation energy, (a) the fraction of ON events increases, (b) the ratio of exciton-detrapping rate/trapping rate increases, and (c) the extent of beneficial hole trapping increases. A relative decrease in PLQY with increasing excitation energy is much less pronounced in CAS QDs than in CS QDs. Unless trap states are removed completely especially in the higher-energy landscape, PLQY will remain inherently dependent on excitation energy for QDs in the vast energy landscape. When reporting the PLQY of QDs, the magnitude of the excitation energy must be mentioned.

Ultrafast dynamics and ultrasensitive single particle spectroscopy of optically robust core/alloy shell semiconductor quantum dots.

A "one-pot one-step" synthesis method of Core/Alloy Shell (CAS) quantum dots (QDs) offers the scope of large scale synthesis in a less time consuming, more economical, highly reproducible and high-throughput manner in comparison to "multi-pot multi-step" synthesis for Core/Shell (CS) QDs. Rapid initial nucleation, and smooth & uniform shell growth lead to the formation of a compositionally-gradient alloyed hetero-structure with very significantly reduced interfacial trap density in CAS QDs. Thus, interfacial strain gets reduced in a much smoother manner leading to enhanced confinement for the photo-generated charge carriers in CAS QDs. Convincing proof of alloy-shelling for a CAS QD has been provided from HRTEM images at the single particle level. The band gap could be tuned as a function of composition, temperature, reactivity difference of precursors, etc. and a high PLQY and improved photochemical stability could be achieved for a small sized CAS QD. From the ultrafast exciton dynamics in CdSe and InP CAS QDs, it has been shown that (a) the hot exciton thermalization/relaxation happens in <500 fs, (b) hot electron trapping dynamics occurs within a ∼1 ps time scale, (c) band edge exciton trapping occurs within a 10-25 ps timescale and (d) for CdSe CAS QDs the hot hole gets trapped in about 35 ps. From fast PL decay dynamics, it has been shown that the amplitude of the intermediate time constant can be correlated with the PLQY. A model has been provided to understand these ultrafast to fast exciton dynamical processes. At the ultrasensitive single particle level, unlike CS QDs, CdSe CAS QDs have been shown to exhibit (a) constancy of PLmax (i.e. no bluing) and (b) constancy of PL intensity (i.e. no bleaching) of the single CAS QDs for continuous irradiation for one hour under an air atmosphere. Thus, CAS QDs hold the promise of being a superior optical probe in comparison to CS QDs both at the ensemble and at the single particle level, leading to enhanced flexibility of the CAS QDs towards designing and developing next generation application devices.

Interacting fermions in two dimension in simultaneous presence of disorder and magnetic field.

We study the revival of Hofstadter butterfly due to the competition between disorder and electronic interaction using mean field approximation of unrestricted Hartree Fock method at zero temperature for two dimensional square and honeycomb lattices. Interplay of disorder and electronic correlation to nullify each other is corroborated by the fact that honeycomb lattice needs more strength of electronic correlation owing to its less co-ordination number which enhances the effect of disorder. The extent of revival of the butterfly is better in square lattice than honeycomb lattice due to higher coordination number. The effect of disorder and interaction is also investigated to study entanglement entropy and entanglement spectrum. We find that for honeycomb lattice area law of entanglement entropy is obeyed in all cases but for square lattice there is some departure from area law for larger subsystems. The entanglement spectrum have the reflection symmetry of the original butterfly of the Hofstadter spectrum. The interaction induces a gap in the entanglement spectrum as well conforming the correspondence between physical spectrum and entanglement spectrum. The effect of disorder closes the interaction induced gap in the entanglement spectrum establishing the nullification of interaction due to disorder and vice versa.

Near-Ergodic CsPbBr3 Perovskite Nanocrystal with Minimal Statistical Aging.

Optical robustness, uniformity, ergodicity, statistical aging, etc. dictate the applicability of nanocrystals. Based on a series of multimodal statistical analyses such as the Kolmogorov-Smirnov test, Lévy statistics, etc., we demonstrate that for CsPbBr3 perovskite nanocrystals (PNCs): (a) the extent of heterogeneity in the quality and associated physical processes is minimal; (b) the optical robustness is very high, and (c) indeed, a single PNC can depict optical behavior of its ensemble. In addition, toward prospective applications, an optically robust CsPbBr3 PNC exhibits (i) near-ergodicity and (ii) minimal statistical aging, which are extremely vital and complementary to its high defect tolerance.

Visible light-induced charge injection and migration in self-assembled carbon dot-DNA-carbon dot nano-dumbbell obtained through controlled stoichiometric conjugation.

The potential of carbon dots (CDs) for photonic conversion to charged states, together with the ability of DNA to transport such charge for extensive charge separation, offers an opportunity to control directionality of migration for photo-induced radical cations in CD-DNA based nano-assemblies. This is achieved through engineering the reaction valency of CDs whereby one CD is covalently conjugated with one ssDNA strand. Subsequently, a CD-DNA-CD nano-dumbbell architecture was created through hybridization mediated self-assembly. The time and intensity-dependent transduction of visible light photonic energy to chemical potential in DNA was achieved through irradiation of 1,4-diaminoathraquinone and glyoxal derived CD with 100 W tungsten source and natural sunlight. Following charge injection by CD, the radical cation migration in DNA was perceived through trapping of the hole in repeated GG steps in the DNA. Overall, a breakthrough in visible-light-induced charge transfer by CD into DNA was achieved, potentially applicable to optobioelectronics.

7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani.

Aim: To analyze the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani. Methods: GNPs were synthesized using DHF and characterized by dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, transmission electron microscopy and x-ray diffraction. The efficacy of DHF and DHF-GNP were tested against sensitive and drug-resistant parasites. GNP uptake was measured on macrophages by atomic absorption spectroscopy. Results: DHF and DHF-GNP (∼35 nm) were equally effective against sensitive and drug-resistant strains and inhibited the arginase activity of parasites. Increased IFN-γ and reduced IL-12 cytokine response showed a Th1/Th2-mediated cell death in macrophages. Conclusion: The low cytotoxicity and high biological activity of DHF-GNP may be useful for chemotherapy of leishmaniasis.

Comparing novel versus conventional technique of platelet-rich plasma therapy in periorbital hyperpigmentation: A randomized prospective split-face study.

BACKGROUND: Platelet-rich plasma (PRP) has been found to be effective in treating periorbital hyperpigmentation (POH). PRP prepared by double-spin (DS) method and activated by calcium has been used conventionally. PRP can be prepared by single spin (SS) and activated at low temperature (novel method), but the evidence is limited. OBJECTIVE: To compare the novel and conventional PRP in the treatment of periorbital hyperpigmentation. METHODS: We selected 21 patients of POH and randomly divided the face into two halves. One-half of the face (group A) was treated with novel PRP (SS and low-temperature activation). The other half (group B) was treated with conventional PRP (DS and calcium activation). A total of 3 PRP injections were given at 4 weekly intervals. Patients were observed and assessed on 12th week by photography, dermoscopy, visual analog scale (VAS) score, and Dermatology life quality index (DLQI). Platelet counts and growth factors were assessed in PRP. RESULTS: Mean platelet count in novel and conventional PRP was 7.41 ± 1.76 lacs and 8.17 ± 2.23 lacs (p = 0.348). Mean photographic and dermoscopic assessment at the end of the study in group A and group B was 52.33 ± 6.468 and 53.14 ± 6.99 (p = 0.151). Change in VAS in groups A and B was 3.85 ± 1.27 and 3.90 ± 1.04 (p = 0.895). Levels of various growth factors assessed by ELISA did not differ significantly. There was significant decline in DLQI. CONCLUSION: The novel method is not inferior to conventional method of PRP in the treatment of periorbital hyperpigmentation.

Unravelling halide-dependent charge carrier dynamics in CsPb(Br/Cl)3 perovskite nanocrystals.

With an increasing bromide content in CsPb(Br/Cl)3 perovskite nanocrystals (PNCs), the steady state photoluminescence quantum yield value increases from 28% to 50% to 76%. Ultrafast transient absorption analyses reveal that the normalized band edge population increases more than two-fold on excitation at the band edge with increasing bromide content, and the hot exciton trapping time increases from 450 fs to 520 fs to 700 fs with increasing bromide content. Ultrasensitive single particle spectroscopic analyses reveal that the peak of the ON fraction distribution increases from 0.65 to 0.75 to 0.85 with increasing bromide content. More specifically, the percentage of PNCs with the ON fraction >75% increases four fold from 24% to 50% to 98% with increasing bromide content. Moreover, the ratio of the detrapping rate and trapping rate increases more than 25 fold with an increase in bromide content, signifying the excitons remaining in the trap state for a smaller time with increasing bromide content. In order to standardize the measurement and analyses, all these three PNCs have the same size and shape, and all the excitations have been made at the same energy above the band edge for all three PNCs and for both ultrafast transient absorption and ultrasensitive single particle measurements.

Clinical Post-operative Bleeding During Minor Oral Surgical Procedure and In Vitro Platelet Aggregation in Patients on Aspirin Therapy: Are they Coherent?

AIM: The risk of excessive bleeding prompts physicians to discontinue aspirin in patients on low-dose, long-term therapy which in turn puts them at the risk from adverse cardiovascular and thrombotic events. Effect of low-dose aspirin therapy on platelet function was assessed using platelet aggregation method. The aim was to correlate the laboratory platelet function with cutaneous and clinical oral bleeding time (BT). MATERIALS AND METHODS: One hundred one patients were enrolled in this prospective trial and were allocated into two groups. Interventional or test group consisted of patients who were on aspirin therapy (75 mg/100 mg) for primary or secondary prevention of angina, myocardial infarction and stroke. Minor oral surgical procedure was performed in this group without discontinuing aspirin therapy. Control group consisted of healthy patients (under no medication) undergoing minor oral surgical procedure. Cutaneous and clinical oral BT were recorded in both the groups. Venous blood sample was drawn, and percentage platelet aggregation function was analysed using adenosine diphosphate (ADP) and arachidonic acid (AA) reagents. The percentage of platelet aggregation was then correlated with cutaneous and clinical oral BT. RESULTS: A significant decrease in percentage platelet aggregation using ADP (aspirin-74.7 21.39; control-89.2 13.70) and AA (aspirin-47.6 23.11; control-82.3 20.17) was observed. However, there were no significant difference in mean cutaneous BT (aspirin-1.5 0.65 min; control-1.6 0.71 min) and clinical oral BT (aspirin-5.0 2.48 min; control-4.8 2.60 min) in aspirin and control groups. CONCLUSION: Majority of the minor oral surgical procedures can be carried out safely without discontinuing aspirin in patients on low-dose long-term therapy. This is possible because despite significant platelet aggregation evident in laboratory evaluation there is lack of its clinical corroboration owing to aspirin resistance. CLINICAL TRIAL REGISTRATION: CTRI/2018/02/012055.