Measurements of Impoverishing and Catastrophic Surgical Health Expenditures in Low- and Middle-Income Countries and Reduction Interventions in the Last 30 years, a Systematic Review.

INTRODUCTION: Approximately 33 million people suffer catastrophic health expenditure (CHE) from surgery and/or anesthesia costs. The aim of this systematic review is to evaluate catastrophic and impoverishing expenditure associated with surgery and anesthesia in low- and middle-income countries (LMICs). METHODS: We performed a systematic review of all studies from 1990 to 2021 that reported CHE in LMICs for treatment of a condition requiring surgical intervention, including cesarean section, trauma care, and other surgery. RESULTS: 77 studies met inclusion criteria. Tertiary facilities (23.4%) were the most frequently studied facility type. Only 11.7% of studies were conducted in exclusively rural health-care settings. Almost 60% of studies were retrospective in nature. The cost of procedures ranged widely, from $26 USD for a cesarean section in Mauritania in 2020 to $74,420 for a pancreaticoduodenectomy in India in 2018. GDP per capita had a narrower range from $315 USD in Malawi in 2019 to $9955 USD in Malaysia in 2015 (Median = $1605.50, interquartile range = $1208.74). 35 studies discussed interventions to reduce cost and catastrophic expenditure. Four of those studies stated that their intervention was not successful, 18 had an unknown or equivocal effect on cost and CHE, and 13 concluded that their intervention did help reduce cost and CHE. CONCLUSIONS: CHE from surgery is a worldwide problem that most acutely affects vulnerable patients in LMICs. Existing efforts are insufficient to meet the true need for affordable surgical care unless assistance for ancillary costs is given to patients and families most at risk from CHE.

MicroRNAs Targeting Critical Molecular Pathways in Diabetic Cardiomyopathy Emerging Valuable for Therapy.

MicroRNAs have emerged as an important regulator of post-transcriptional gene expression studied extensively in many cancers, fetal development, and cardiovascular diseases. Their endogenous nature and easy manipulation have made them potential diagnostic and therapeutic molecules. Diseases with complex pathophysiology such as Diabetic Cardiomyopathy display symptoms at a late stage when the risk of heart failure has become very high. Therefore, the utilization of microRNAs as a tool to study pathophysiology and device-sustainable treatments for DCM could be considered. The present review focuses on the mechanistic insights of diabetic cardiomyopathy and the potential role of microRNAs.

Incidence of Morphological Defects in Sperm of Mice Exposed to Hospital Effluent.

Hospital effluents are loaded with drugs, radioactive elements, pathogens, etc. Effluents from treatment plants at source sites may get mixed up with potable water, leading to numerous detrimental/toxic effects. In this study, efforts were made to investigate the toxic effects of one such effluent from a local hospital on the reproductive characteristics of mice when orally administered daily for 60 consecutive days. We primarily focused on the changes in the morphology of the sperm and its geometric morphometrics, i.e., sperm head length and width, area, and perimeter, measured using ImageJ software. The incidence of sperm defects was recorded, and variations in the morphometrics were analyzed by one-way ANOVA using Tukey's post hoc test. A physico-chemical characterization of the water samples was also performed to assess the basic water quality. In summary, the study revealed the critical role of treated water in inducing different abnormalities in sperm, such as the absence of a head, bent necks, abnormal neck attachment, highly coiled tails, and missing tails. Significant differences (p < 0.01 **, p < 0.001 ***) in the morphometrics of spermatozoa with banana heads, hammer heads, missing heads, pin heads, and missing hooks were noted compared to corresponding controls. It could thus be concluded that treated hospital effluent is still inadequately clean and contains significant amounts of toxicants that might be detrimental to sperm quality.

Global Neurosurgery: Progress and Resolutions at the 75th World Health Assembly.

Neurosurgical advocates for global surgery/neurosurgery at the 75th World Health Assembly gathered in person for the first time after the COVID-19 pandemic in Geneva, Switzerland, in May 2022. This article reviews the significant progress in the global health landscape targeting neglected neurosurgical patients, emphasizing high-level policy advocacy and international efforts to support a new World Health Assembly resolution in mandatory folic acid fortification to prevent neural tube defects. The process of developing global resolutions through the World Health Organization and its member states is summarized. Two new global initiatives focused on the surgical patients among the most vulnerable member states are discussed, the Global Surgery Foundation and the Global Action Plan on Epilepsy and other Neurological Disorders. Progress toward a neurosurgery-inspired resolution on mandatory folic acid fortification to prevent spina bifida-folate is described. In addition, priorities for moving the global health agenda forward for the neurosurgical patient as it relates to the global burden of neurological disease are reviewed after the COVID-19 pandemic.

Patient and Surgeon Perceptions Regarding Microdiscectomy Surgery: A Cross-Sectional Analysis of Social Media Posts.

BACKGROUND: Social media offers a powerful and expanding platform for sharing the patient experience with a large audience through an unsolicited perspective. The content may influence future perceptions around surgical care. OBJECTIVE: To analyze publicly available content on a major social media outlet related to microdiscectomy surgery based on perspective, location, timing, content, tone, and patient satisfaction. METHODS: A query of content was performed for the study period 1 January 2019 to 1 January 2021. Relevant content was identified by hashtag "#microdiscectomy." The initial query returned 10,050 publicly available posts, and the 1500 most "liked" posts were included for evaluation. Content was subsequently classified, characterized, and analyzed. RESULTS: Patients created 72.9% of microdiscectomy-related content, and spine surgeons created 23.5%. Regarding region, 77.0% of posts originated in the United States. The majority portrayed the patient experience in the postoperative phase of care (86.0%), with the primary reference to activities of daily living (56.9%). Only 1.7% of posts depicted the surgical incision site. The connotation of posts was deemed positive in 78.5% of cases. Of the posts referencing satisfaction, 98.3% depicted patient satisfaction with the surgical outcome. Patient posts in the postoperative phase of care (>1 week after surgery) were more than 2 times as likely to express positive tone (OR = 2.07, P ≤ 0.013) with their clinical course compared with patient posts outside the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, social media posts are written in a positive tone, express satisfaction with surgical outcome, typically occur in the postoperative period of care, and depict activities of daily living. These popular mechanisms of communication, such as Instagram, offer spine surgeons unique insights into the true patient experience and may provide an opportunity for surgeons to assess patient feedback, influence patient perceptions, and enhance delivery of lumbar spine care.

Monitoring hospital effluents through physico-chemical characterization and genotoxic testing.

Inefficient monitoring of the water resource recovery facility at various health care establishments may lead to detrimental effects on human population, especially when such water get mixed with potable municipal water supply. To ensure the efficiency and proper functioning of the water resource recovery facility and quality of water, before it being disposed of, the present study was conducted with the assessment of physico-chemical parameters of water and its genotoxic and cytogenetic effects in mice. The sample water was given ad libitum to animals for three different time durations, that is, 7, 15, and 30 days. Bone marrow chromosomal aberration and bone marrow micronucleus (MN) assay were performed to get the extent of genotoxicity and cytogenicity. The results showed presence of chromosomal aberrations like fragments breaks and ring formation in different groups. Besides this, a significant (p < 0.05*, p < 0.01**, p < 0.001***) decrease in the mitotic index was noted in the group which was given 100% concentrated sample water for 30 days. A significant (p < 0.05*, p < 0.01**, p < 0.001***) increase in MN induction and decreased ratio of polychromatic to normochromatic erythrocytes were observed in groups which were given samples at 10% and 100% concentrations for longer durations. The findings suggest that even the recovered sample water reflects a positive in vivo genotoxic potential when given for a longer duration of 30 days, indicating some lacuna in the treatment process.

Investigating microRNAs in diabetic cardiomyopathy as tools for early detection and therapeutics.

To profile microRNAs population of glucose-induced cardiomyoblast cell line and identify the differentially expressed microRNAs and their role under pre-diabetes and diabetes condition in vitro. Rat fetal ventricular cardiomyoblast cell line H9c2 was treated with D-glucose to mimic pre-diabetic, diabetic, and high-glucose conditions. Alteration in cellular, nuclear morphology, and change in ROS generation was analyzed through fluorescent staining. Small RNA sequencing was performed using Illumina NextSeq 550 sequencer and was validated using stem-loop qRT-PCR. A large number (~ 100) differential miRNAs were detected in each treated samples as compared to control; however, a similar expression pattern was observed between pre-diabetes and diabetes conditions with the exception for miR-429, miR-101b-5p, miR-503-3p, miR-384-5p, miR-412-5p, miR-672-5p, and miR-532-3p. Functional annotation of differential expressed target genes revealed their involvement in significantly enriched key pathways associated with diabetic cardiomyopathy. For the first time, we report the differential expression of miRNAs (miR-1249, miR-3596d, miR- 3586-3p, miR-7b-3p, miR-191, miR-330-3p, miR-328a, let7i-5p, miR-146-3p, miR-26a-3p) in diabetes-induced cardiac cells. Hyperglycemia threatens the cell homeostasis by dysregulation of miRNAs that begins at a glucose level 10 mM and remains undetected. Analysis of differential expressed miRNAs in pre-diabetes and diabetes conditions and their role in regulatory mechanisms of diabetic cardiomyopathy holds high potential in the direction of using miRNAs as minimally invasive diagnostic and therapeutic tools.

Synthesis of Novel Bis-imino and Bis-amino Curcuminoids for Evaluation of Their Anticancer and Antibacterial Activity.

A new set of curcumin analogues with a Schiff base moiety were synthesized from a bis-aldehyde derivative of hydroxybenzylidene cyclohexanone and various alicyclic and aromatic amines. The single crystals of compound 2 (bis-aldehyde), compound 3b (bis-cyclohexylimino derivative), and compound 3c (bis-1-imino piperidyl derivative) were developed. The said bis-imino and bis-amino curcuminoids were tested for anticancer activity against MCF-7 utilizing the conventional MTT assay. These Schiff bases had significantly higher anticancer efficacy than curcumin and methotrexate against MCF-7 cell lines. Compounds 3k, 3b, and 3l have the highest efficacy among all synthesized curcuminoids. The MTT results are in accordance with the binding affinities found by docking the said molecules with HER2 Tyrosine Kinase (HER2-TK). Compound 3b is identified as a promising HER2-TK inhibitor and also shows effective inhibition against Gram-positive bacteria Staphylococcus aureus.

Proteomic Analysis of Glucose-Induced Cardiac Myoblasts and the Potential Role of mir-92b-5p in Regulating Sarcomere Proteins Under a Hyperglycemic Environment.

BACKGROUND: Diabetes mellitus, a common metabolic disorder that causes high blood glucose, is due to impaired insulin secretion. Prolonged high blood sugar is associated with heart disease. Many proteins are involved in metabolic pathways and contractility of cardiac cells regulate cardiac hypertrophy, altering normal cardiac physiology and function. Moreover, microRNAs are essential regulators of these proteins. Thus, there is a need to study the protein and microRNA alterations in cardiomyocytes to better understand the mechanisms activated during cardiac stress. OBJECTIVE: The study aims to profile differentially expressed sarcomere proteins in H9C2 cell lines under high glucose conditions compared with normal conditions, along with the identification of miRNAs regulating these proteins. METHODS: Cardiac myoblast cell lines were treated with D-Glucose at three concentrations (10 mM, 25 mM, and 50 mM). Total cell protein was analyzed by Tandem Mass spectrometry Nano LCMS/ MS. Furthermore, next-generation sequencing data were analyzed for detecting microRNAs regulating cardiac cell protein expression. Bioinformatics databases such as Uniprot, Ingenuity Pathway Analysis (IPA), PANTHER, and Target scan were used. RESULTS: The Nano LC-MS/MS analysis showed 2891 protein, 1351 protein groups, and 4381 peptide groups in both glucose-treated and control samples. Most proteins were metabolite interconversion enzymes, translation proteins, and proteins regulating the cytoskeleton. IPA analysis revealed differentially expressed proteins involved in EIF2 signaling, actin cytoskeleton signaling, cardiac fibrosis, and cell death. Moreover, the proteins troponin, tropomyosin, myosin, alpha-actin, and ATP synthase were found to be downregulated, thus responsible for altering sarcomere protein expression. Rno-mir-92b-5p was observed to be highly upregulated at 50 mM. Its target genes namely TPM2, ATP1A2, and CORO1C were mostly components of the sarcomere complex and its regulators. CONCLUSION: A combination of proteomic profile and microRNA profile of hyperglycemic cells provides an insight into advanced therapeutics. Our study has highlighted the role of sarcomere proteins, activation of Eukaryotic Initiation Factor 2 (EIF2) signaling, and suppression of actin cytoskeleton signaling in the pathophysiology of cardiomyopathy. MiR-92b-5p has an important role in regulating sarcomere protein complex activated.

Assessment of genotoxic potential of the treated hospital wastewater using cytogenetic assays.

The cytogenetic study using hospital effluent was carried out engaging three cytogenetic end points-chromosomal aberration (CA) assay, mitotic indices (MIs), and micronucleus (MN) Analysis. These bioassays were performed in hematopoietic bone marrow cells of Mus musculus. The experiment commenced with the collection of hospital effluent from the final outlet when wastewater gets collected after undergoing treatment by a multistep process. The pure treated sample water was collected at different times between March 2019 to January 2020 and was given ad libitum to mice at its low (90% dilution) and high (pure form), i.e. 100% concentration for 3 different durations i.e. 7, 15, and 30 days, respectively. The results indicated a significant (P < 0.01) decrease in the MI in all the groups but was more pronounced in the group which was given 100% concentrated sample water collected in the month of March 2019. Besides this, the major finding was presence of CAs like breaks, fragments, rings, and pulverization in bone marrow cells in different groups; however, the frequency of these aberrations varied from group to group. A significant (P < 0.01) increase in MN Induction and decreased ratio (P < 0.01) of polychromatic to normonochromatic erythrocytes were observed in samples collected in month of March both at 10% and 100% concentrations. However, decrease in the ratio was observed in the samples of September and January at low-concentration sample water. The results thus indicated that there was some lacuna in the treatment process earlier in the month of March, which was rectified to some extent in the subsequent months. Hence, the treated wastewater collected in the month of January next year was more suitable for its use than other samples. Summary: These findings thus draw attention toward ensuring efficiency of the treatment plant and quality of water by the hospital management before it being disposed off into the municipal supply; a step that can help society to live a healthy life. With these findings, it is conveyed that all the hospitals, diagnostic labs, and other health care establishments must pay utmost attention at liquid waste disposal mechanism to make environment pollution-free.

Aloe vera protects against fluoride-induced teratogenic effects during pre- and postnatal development in mice.

Pregnancy and feto-gestational toxicities on exposure to fluoride and its possible amelioration on co-administration with aloe vera were studied in pregnant Swiss albino mice. Once the confirmed pregnancy was tested, animals were equally divided into four groups as follows: group I was given no treatment and served as control, and groups II and III were administered with 100 and 300 ppm sodium fluoride, respectively, while group IV was co- administered aloe vera (300 mg/kg bw) along with sodium fluoride (300 ppm) daily for 14 days prior to gestation and continued till the 18th day of gestation. Animals were sacrificed on the 19th day of gestation for prenatal observations. Maternal body weight, the gravid uterine weight, number of corpora lutea in both the ovaries, number of implantations and resorptions, number of live (mature and immature) fetuses, and number of dead fetuses were examined in each dam. The treatment continued in another set of animals till the completion of the weaning period to observe postnatal changes due to test substances on the mother and pups. Sodium fluoride-treated animals showed morphometric and skeletal changes which were more pronounced in the high-dose group showing significantly decreased body weight gain in pregnant mothers and dead/immature fetuses. Morphometric changes included open eyelids, limb defects, wrinkles on the whole body, anophthalmia, pulmonary edema, enlarged esophagus, and decreased body weight of fetuses and pups. Alizarin-prepared skeletal structures of fetuses of such female mice showed delayed ossification or bending in the number of bones of skull, thoracic, and limb regions. However, concomitant exposure to sodium fluoride and aloe vera in treated animals led to a marked improvement in all the prenatal and postnatal variables. The study suggests that sodium fluoride at high concentrations may be teratogenic while co-administration of aloe vera during fluoride exposure might be beneficial in reducing these toxic effects. The use of aloe vera as a preventive agent or as a complimentary agent is thus recommended following fluoride exposure through the oral route.

Inter-Patient Atrial Flutter Classification Using FFT-Based Features and a Low-Variance Stacking Classifier.

OBJECTIVE: Atrial Flutter (AFL) is a supraventricular tachyarrhythmia typically arising from a macroreentry circuit that can have variable atrial anatomy. It is often treated by catheter ablation, the success of which depends upon the correct determination of the electroanatomic circuit, generally through invasive electrophysiological (EP) study. We hypothesized that machine learning (ML) methods applied to the diagnostic 12-lead surface electrocardiogram (ECG) could determine the specific circuit prior to any invasive EP study. METHODS: The 12-lead ECGs were reduced to eight independent leads: I, II, V1 - V6. Through an algorithm using ventricular complex cancellation methods, windows of atrial activity in the ECG were uncovered and spectra were generated. Three ML classifier approaches were applied: Support Vector Machine (SVM), Random Forest (RF) and k-Nearest Neighbors (KNN), and their outputs combined using soft voting. RESULTS: Ten-second surface ECGs taken from 419 AFL patients prior to invasive EP study and ablation were analyzed retrospectively. Of the 419 patients, 285 had typical cavotricuspid isthmus (CTI)-dependent AFL, 41 had atypical right-atrial AFL and 93 had left-atrial AFL, as determined during the subsequent EP study. Lead V5 was found to be most useful giving a test accuracy of 98% and f1 score of 0.97. CONCLUSION: We conclude that ML methods have the potential to automatically determine the AFL macroreentry circuit from the surface ECG. SIGNIFICANCE: The AFL classification method presented in this investigation achieves 95+% accuracy on an unbalanced inter-patient dataset which has important clinical applications.

MicroRNAs: A Critical Regulator and a Promising Therapeutic and Diagnostic Molecule for Diabetic Cardiomyopathy.

The risk of heart failure is 2-5 times higher in diabetic patients as compared to non-diabetic patients with similar comorbidities. Recent reports suggest that nearly half of the diabetic population remains undiagnosed, making diabetic cardiomyopathy (DCM) a clinically relevant entity. In the myocardium, chronic hyperglycemia elicits structural and functional abnormalities characterized by ventricular dilation, diastolic dysfunction, fibrosis, and hypertrophy leading to heart failure. Since diabetes is a multifactorial heterogeneous metabolic disorder which cannot be diagnosed or controlled along with coronary artery disease or hypertension, there is an urgent need to understand the underlying molecular mechanisms that leads to DCM and identify potential therapeutic targets. Small non-coding RNAs, in particular, microRNAs (miRNAs), have emerged as key regulators for several life-threatening diseases, including DCM. Recent studies have reported that miRNAs not only regulate the fundamental mechanisms of DCM such as insulin resistance, MAPK pathway, PI3K-AkT pathway, oxidative stress, also inflammatory signaling, but also possess the potential to be a therapeutic or diagnostic target. This review examines the role of critical miRNAs in the onset and pathogenesis of DCM, which also depicts high potential as therapeutic and diagnostic molecule in preclinical studies. Further, it highlights the completed and on-going clinical trials around the globe for diabetes and miRNAs to provide a outlook about the upcoming miRNA therapeutics.

Identification and expression analysis of conserved microRNAs during short and prolonged chromium stress in rice (Oryza sativa).

MicroRNAs (miRNAs) are one of the most critical epigenetic regulators of gene expression which modulate a spectrum of development and defence response processes in plants. Chromium (Cr) contamination in rice imposes a serious concern to human health as rice is used as staple food throughout the world. Although several studies have established the differential response of miRNAs in rice during heavy metal (arsenic, cadmium) and heat or cold stress, no report is available about the response of miRNAs during Cr stress. In the present study, we identified 512 and 568 known miRNAs from Cr treated and untreated samples, respectively. Expression analysis revealed that 13 conserved miRNAs (miR156, miR159, miR160, miR166, miR169, miR171, miR396, miR397, miR408, miR444, miR1883, miR2877, miR5072) depicted preferential up- or down-regulation (> 4-fold change; P value < 0.05). Target gene prediction of differentially expressed miRNAs and their functional annotation suggested the important role of miRNAs in defence and detoxification of Cr though ATP-binding cassette transporters (ABC transporters), transcription factors, heat shock proteins, auxin response, and metal ion transport. Real-time PCR analysis validated the differential expression of selected miRNAs and their putative target genes. In conclusion, our study identifies and predicts miRNA-mediated regulation of signalling pathway in rice during Cr stress.

Differential expression of novel MicroRNAs from developing fetal heart of Gallus gallus domesticus implies a role in cardiac development.

Heart development is a complex process regulated by multi-layered genetic as well epigenetic regulators many of which are still unknown. Besides their critical role during cardiac development, these molecular regulators emerge as key modulators of cardiovascular pathologies, where fetal cardiac genes' re-expression is witnessed. MicroRNAs have recently emerged as a crucial part of signalling cascade in both development and diseases. We aimed to identify, validate, and perform functional annotation of putative novel miRNAs using chicken as a cardiac development model system. Novel miRNAs were obtained through deep sequencing of small RNAs extracted from chicken embryonic cardiac tissue of different developmental stages. After filtering out real pre-miRNAs, their expression analysis, potential target gene's prediction and functional annotations were performed. Expression analysis revealed that miRNAs were differentially expressed during different developmental stages of chicken heart. The expression of selected putative novel miRNAs was further validated by real-time PCR. Our analysis indicated the presence of novel cardiac miRNAs that might be regulating critical cardiac development events such as cardiac cell growth, differentiation, cardiac action potential generation and signal transduction.

Microbial Mutagenicity Assay: Ames Test.

The Microbial mutagenicity Ames test is a bacterial bioassay accomplished in vitro to evaluate the mutagenicity of various environmental carcinogens and toxins. While Ames test is used to identify the revert mutations which are present in strains, it can also be used to detect the mutagenicity of environmental samples such as drugs, dyes, reagents, cosmetics, waste water, pesticides and other substances which are easily solubilized in a liquid suspension. We present the protocol for conducting Ames test in the laboratory.

Degradation of phorbol esters by Pseudomonas aeruginosa PseA during solid-state fermentation of deoiled Jatropha curcas seed cake.

Large amount of seed cake is generated as by-product during biodiesel production from Jatropha seeds. Presence of toxic phorbol esters restricts its utilization as livestock feed. Safe disposal or meaningful utilization of this major by-product necessitates the degradation of these phorbol esters. The present study describes the complete degradation of phorbol esters by Pseudomonas aeruginosa PseA strain during solid state fermentation (SSF) of deoiled Jatropha curcas seed cake. Phorbol esters were completely degraded in nine days under the optimized SSF conditions viz. deoiled cake 5.0 g; moistened with 5.0 ml distilled water; inoculum 1.5 ml of overnight grown P. aeruginosa; incubation at temperature 30 °C, pH 7.0 and RH 65%. SSF of deoiled cake seems a potentially viable approach towards the complete degradation of the toxic phorbol esters.