A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.

TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify potentially pathogenic variants causing PCD and multiple morphological abnormalities of sperm flagella (MMAF) in an infertile Pakistani man. Diagnostic imaging techniques were used for PCD screening in the patient. Real-time polymerase chain reaction (RT‒PCR) was performed to detect the effect of mutations on the mRNA abundance of the affected genes. Papanicolaou staining and scanning electron microscopy (SEM) were carried out to examine sperm morphology. Transmission electron microscopy (TEM) was performed to examine the ultrastructure of the sperm flagella, and the results were confirmed by immunofluorescence staining. Using WES and Sanger sequencing, a novel homozygous missense variant (c.C1069T; p.Arg357Trp) in TTC12 was identified in a patient from a consanguineous family. A computed tomography scan of the paranasal sinuses confirmed the symptoms of the PCD. RT-PCR showed a decrease in TTC12 mRNA in the patient's sperm sample. Papanicolaou staining, SEM, and TEM analysis revealed a significant change in shape and a disorganized axonemal structure in the sperm flagella of the patient. Immunostaining assays revealed that TTC12 is distributed throughout the flagella and is predominantly concentrated in the midpiece in normal spermatozoa. In contrast, spermatozoa from patient deficient in TTC12 showed minimal staining intensity for TTC12 or DNAH17 (outer dynein arms components). This could lead to MMAF and result in male infertility. This novel TTC12 variant not only illuminates the underlying genetic causes of male infertility but also paves the way for potential treatments targeting these genetic factors. This study represents a significant advancement in understanding the genetic basis of PCD-related infertility.

Evaluation of pediatric patients for intestinal transplantation in the modern era.

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

Analyzing the impact of pesticides on the indus river: contamination levels in water, sediment, fish, and associated human health risks.

Pesticides are frequently used to protect crop yields and manage malaria vectors; however, their inadvertent transport into aquatic habitats poses a significant concern. Various anthropogenic activities influence the Indus River in Pakistan. This study aimed to assess the presence of eight pesticide residues at three different sites (Kalabagh, Kundian, and Chashma) in water, sediment, and the fish species (Labeo rohita) during both dry and wet seasons to measure the intensity of this pressure. Pesticide analysis was carried out using gas chromatography equipped with an electron capture detector. The results revealed the highest concentrations of pesticides during both dry and wet seasons at all sites, measuring 0.83 and 0.62 µg/l (water), 12.37 and 9.20 µg/g/dw (sediment), and 14.27 and 11.29 µg/g/ww (L. rohita), respectively. Overall, pesticide concentrations were higher in the dry season than in the wet season across all study sites. Based on detection frequency and concentration in both seasons at all sites, dominant pesticides included cypermethrin and carbofuran (in water), as well as endosulfan and cypermethrin (in sediment and fish tissue). Levels of endosulfan and cypermethrin exceeded standard limits. Moreover, principal component analysis (PCA) indicated no correlation among pesticides in fish tissue, sediment, and water. However, pesticides exhibited different behavior in different seasons. Furthermore, endosulfan and triazophos impose great human health risk, as indicated by the THQ value (> 1). The overall HI value was greater for site 1 in the dry season (8.378). The study concluded that the presence of agricultural pesticides in the Indus River poses a risk to aquatic life and has the potential to disrupt the entire food chain. This highlights the importance of sustainable practices for the study area and Pakistan overall agricultural and environmental sustainability. It is further recommended to strengthen regulations for reduced pesticide use and promote eco-friendly pest management.

Exploring the effect of different application rates of biochar on the accumulation of nutrients and growth of flue-cured tobacco (Nicotiana tabacum).

Background: Biochar application has become one of the most potential tools to improve soil fertility and plant growth for sustainable and eco-friendly agriculture. However, both positive and negative effects of biochar application have been recorded on plant growth and soil fertility. Methods: This study investigated the impact of different application rates (0, 600, 900, 1200, and 1800 kg/ha) of biochar on the soil nutrient contents, accumulation of nutrients and dry matter in different plant parts, and growth of flue-cured tobacco plants under field conditions. Results: Results demonstrated that soil organic carbon pool and carbon/nitrogen ratio were increased proportionally with the increasing dosage of biochar, 25.54 g/kg and 14.07 g/kg compared with control 17 g/kg and 10.13 g/kg, respectively. The contents of soil total nitrogen were also significantly increased after biochar application in the middle (1.77 g/kg) and late-growth (1.54 g/kg) stages of flue-cured tobacco than in control (1.60 g/kg and 1.41 g/kg, respectively). The contents of soil nitrate nitrogen were also higher under low (600 and 900 kg/ha) application rates of biochar and reduced when higher (1200 and 1800 kg/ha) dosages of biochar were applied. However, it was observed that varying application rates of biochar had no impact on soil ammonium nitrogen content during the growth period of flue-cured tobacco plants. The nutrient accumulation (N, P, K) in different parts of flue-cured tobacco plants was significantly increased under a low application rate of biochar, which enhanced the soil and plant analyzer development values, effective leaves number, growth, dry matter accumulation, and leaf yield of flue-cured tobacco. In contrast, the high biochar application rate (1200 and 1800 kg/ha) negatively impacted nutrient accumulation and growth of flue-cured tobacco. Conclusion: Conclusively, the optimum application of biochar (600 and 900 kg/ha) is beneficial for plant growth, soil fertility, accumulation of nutrients, and dry matter in different plant parts. However, excessive biochar application (> 900 kg/ha) could inhibit flue-cured tobacco plant growth. This study provides a theoretical foundation for biochar application in tobacco and other crop production to obtain agricultural sustainability and economic stability.

Suppressor T helper type 17 cell responses in intestinal transplant recipients with allograft rejection.

BACKGROUND: Intestinal transplant (ITx) rejection is associated with memory T helper type 17 cell (Th17) infiltration of grafted tissues. Modulation of Th17 effector cell response is facilitated by T regulatory (Treg) cells, but a phenotypic characterization of this process is lacking in the context of allograft rejection. METHODS: Flow cytometry was performed to examine the expression of surface receptors, cytokines, and transcription factors in Th17 and Treg cells in ITx control (n = 34) and rejection patients (n = 23). To elucidate key pathways guiding the rejection biology, we utilized RNA sequencing (RNAseq) and assessed epigenetic stability through pyrosequencing of the Treg-specific demethylated region (TSDR). RESULTS: We found that intestinal allograft rejection is characterized by Treg cellular infiltrates, which are polarized toward Th17-type chemokine receptor, ROR-γt transcription factor expression, and cytokine production. These Treg cell subsets have maintained epigenetic stability, as defined by FoxP3-TSDR methylation status, but displayed upregulation of functional Treg and purinergic signaling genes by RNAseq analysis such as CD39, in keeping with suppressor Th17 properties. CONCLUSION: We show that ITx rejection is associated with increased polarized cells that express a Th17-like phenotype concurrent with regulatory purinergic markers.

Cereal sprout-based food products: Industrial application, novel extraction, consumer acceptance, antioxidant potential, sensory evaluation, and health perspective.

Cereal grains are a good source of macronutrients and micronutrients that are required for metabolic activity in the human body. Sprouts have been studied to enhance the nutrient profile. Moreover, secondary metabolites are examined as green food engineering technology that is used in the pharmaceutical, functional ingredients, nutraceutical, and cosmetic industries. The sprout-based food is commonly used to enhance the quality of products by softening the structure of the whole grain and increasing the phytochemicals (nutritional value and bioactive compounds). These sprouting grains can be added to a variety of products including snacks, bakery, beverage, and meat. Consuming whole grains has been shown to reduce the incidence and mortality of a variety of chronic and noncommunicable diseases. Sprouting grains have a diversity of biological functions, including antidiabetic, antioxidant, and anticancer properties. Cereal sprout-based products are more beneficial in reducing the risk of cardiovascular diseases and gastrointestinal tract diseases. The novel extraction techniques (microwave-existed extraction, pulse electric field, and enzyme-associated) are applied to maintain and ensure the efficiency, safety, and nutritional profile of sprout. Nutrient-dense sprouts have a low environmental impact and are widely accepted by consumers. This review explores for the first time and sheds light on the antioxidant potential, sensory evaluation, industrial applications, and health perspective of cereal sprout-based food products.

Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.

The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.

Computational analysis of bevacizumab binding with protein receptors for its potential anticancer activity.

Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. In this study, we investigated the binding free energy (ΔG) of bevacizumab, an anti-cancer therapy targeting angiogenesis through the inhibition of vascular endothelial growth factor (VEGF), with various proto-oncogenes including CDK4, EGFR, frizzled, IGFR, OmoMYC, and KIT. Our in-silico investigation revealed that hydrogen bonding is pivotal in inducing conformational changes within the DNA structure, impeding its replication and preventing cell death. Molecular docking results revealed the presence of crucial hydrogen bonds and supported the formation of stable bevacizumab complexes. The molecular docking scores for the tested complexes were CDK4 (Score = -7.2 kcal/mol), EGFR (Score = -8.5 kcal/mol), frizzled (Score = -6.9 kcal/mol), IGFR (Score = -7.8 kcal/mol), KIT (Score = -6.5 kcal/mol), and MYC (Score = -8.3 kcal/mol). The binding mode demonstrated vital hydrogen bonds correlated with the observed energy gap. Notably, the calculated binding free energies of the tested compounds are as follows: CDK4 (ΔG = 24275.195 ± 6411.293 kJ/mol), EGFR (ΔG = 363273.625 ± 8731.466 kJ/mol), frizzled (ΔG = 181751.990 ± 28438.515 kJ/mol), IGFR (ΔG = 162414.725 ± 10728.367 kJ/mol), KIT (ΔG = 40162.585 ± 4331.017 kJ/mol), and MYC (ΔG = 434783.463 ± 53989.676 kJ/mol). Furthermore, through extensive 100 ns MD simulations, we observed the formation of a stable bevacizumab complex structure. The simulations confirmed the stability of the bevacizumab complex with the proto-oncogenes. The results of this study highlight the potential of bevacizumab complex as a promising candidate for anticancer treatment. The identification of hydrogen bonding, along with the calculated binding free energies and molecular docking scores, provides valuable insights into the molecular interactions and stability of the bevacizumab complexes. These findings and the extensive MD simulations open new avenues for future research and development of bevacizumab as a targeted therapy for breast cancer and other related malignancies.Communicated by Ramaswamy H. Sarma.

Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies.

BACKGROUND: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies. AIM: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches. METHODS: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program. RESULTS: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-ß in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue. CONCLUSION: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

Potential anti-amoebic effects of synthetic 1,4-benzothiazine derivatives against Acanthamoeba castellanii.

A rare but lethal central nervous system disease known as granulomatous amoebic encephalitis (GAE) and potentially blinding Acanthamoeba keratitis are diseases caused by free-living Acanthamoeba. Currently, no therapeutic agent can completely eradicate or prevent GAE. Synthetic compounds are a likely source of bioactive compounds for developing new drugs. This study synthesized seventeen 1,4-benzothiazine derivatives (I -XVII) by a base-catalyzed one-pot reaction of 2-amino thiophenol with substituted bromo acetophenones. Different spectroscopic techniques, such as EI-MS, 1H-, and 13C NMR (only for the new compounds), were used for the structural characterization and conformation of compounds. These compounds were assessed for the first time against Acanthamoeba castellanii. All compounds showed anti-amoebic potential in vitro against A. castellanii, reducing its ability to encyst and excyst at 100 µM. Compounds IX, X, and XVI showed the most potent activities among all derivatives and significantly reduced the viability to 5.3 × 104 (p < 0.0003), 2 × 105 (p < 0.006), and 2.4 × 105 (p < 0.002) cells/mL, respectively. The cytotoxicity profile revealed that these molecules showed lower to moderate cytotoxicity, i.e., 36 %, 2 %, and 21 %, respectively, against human keratinocytes in vitro. These results indicate that 1,4-benzothiazines showed potent in vitro activity against trophozoites and cysts of A. castellanii. Hence, these 1,4-benzothiazine derivatives should be considered to develop new potential therapeutic agents against Acanthamoeba infections.

Current Advances in Graft-versus-host Disease After Intestinal Transplantation.

Graft-versus-host disease (GvHD) remains a potentially fatal complication following intestinal transplant (ITx). Over the past decade, advances in the understanding of the pathophysiology of this complex immunological phenomenon have led to the reassessment of the host systemic immune response and have created a gateway for novel preventive and therapeutic strategies. Although sufficient evidence dictates the use of corticosteroids as a first-line option, the treatment for refractory disease remains contentious and lacks a standardized therapeutic approach. Timely diagnosis remains crucial, and the advent of chimerism detection and immunological biomarkers have transformed the identification, prognostication, and potential for survival after GvHD in ITx. The objectives of the following review aim to discuss the clinical and diagnostic features, pathophysiology, advances in immune biomarkers, as well as therapeutic opportunities in the prevention and treatment of GvHD in ITx.

Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.

Co-metabolic degradation and metabolite detection of hexabromocyclododecane by Shewanella oneidensis MR-1.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant; however, it is a persistent organic pollutant as well as affects the human thyroid hormones and causes cancer. However, the degradation of HBCD has received little attention from researchers. Due to its bioaccumulative and hazardous properties, an appropriate strategy for its remediation is required. In this study, we investigated the biodegradation of HBCD using Shewanella oneidensis MR-1 under optimized conditions. The Box-Behnken design (BBD) was implemented for the optimization of the physical degradation parameters of HBCD. S. oneidensis MR-1 showed the best degradation performance at a temperature of 30 °C, pH 7, and agitation speed of 115 rpm, with an HBCD concentration of 1125 µg/L in mineral salt medium (MSM). The strain tolerated up to 2000 µg/L HBCD. Gas chromatography-mass spectrometry analysis identified three intermediates, including 2-bromo dodecane, 2,7,10-trimethyldodecane, and 4-methyl-1-decene. The results provide an insightful understanding of the biodegradation of HBCD by S. oneidensis MR-1 under optimized conditions and could pave the way for further eco-friendly applications. KEY POINTS: • HBCD biodegradation by Shewanella oneidensis • Optimization of HBCD biodegradation by the Box-Behnken analysis • Identification of useful metabolites from HBCD degradation.

BIR: Biomedical Information Retrieval System for Cancer Treatment in Electronic Health Record Using Transformers.

The rapid growth of electronic health records (EHRs) has led to unprecedented biomedical data. Clinician access to the latest patient information can improve the quality of healthcare. However, clinicians have difficulty finding information quickly and easily due to the sheer data mining volume. Biomedical information retrieval (BIR) systems can help clinicians find the information required by automatically searching EHRs and returning relevant results. However, traditional BIR systems cannot understand the complex relationships between EHR entities. Transformers are a new type of neural network that is very effective for natural language processing (NLP) tasks. As a result, transformers are well suited for tasks such as machine translation and text summarization. In this paper, we propose a new BIR system for EHRs that uses transformers for predicting cancer treatment from EHR. Our system can understand the complex relationships between the different entities in an EHR, which allows it to return more relevant results to clinicians. We evaluated our system on a dataset of EHRs and found that it outperformed state-of-the-art BIR systems on various tasks, including medical question answering and information extraction. Our results show that Transformers are a promising approach for BIR in EHRs, reaching an accuracy and an F1-score of 86.46%, and 0.8157, respectively. We believe that our system can help clinicians find the information they need more quickly and easily, leading to improved patient care.

Alpha-Mangostin and its nano-conjugates induced programmed cell death in Acanthamoeba castellanii belonging to the T4 genotype.

Acanthamoeba are free living amoebae that are the causative agent of keratitis and granulomatous amoebic encephalitis. Alpha-Mangostin (AMS) is a significant xanthone; that demonstrates a wide range of biological activities. Here, the anti-amoebic activity of α-Mangostin and its silver nano conjugates (AMS-AgNPs) were evaluated against pathogenic A. castellanii trophozoites and cysts in vitro. Amoebicidal assays showed that both AMS and AMS-AgNPs inhibited the viability of A. castellanii dose-dependently, with an IC50 of 88.5 ± 2.04 and 20.2 ± 2.17 µM, respectively. Both formulations inhibited A. castellanii-mediated human keratinocyte cell cytopathogenicity. Functional assays showed that both samples caused apoptosis through the mitochondrial pathway and reduced mitochondrial membrane potential and ATP production, while increasing reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome-c reductase in the cytosol. Whole transcriptome sequencing of A. castellanii showed the expression of 826 genes, with 447 genes being up-regulated and 379 genes being down-regulated post treatment. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority of genes were linked to apoptosis, autophagy, RAP1, AGE-RAGE and oxytocin signalling pathways. Seven genes (PTEN, H3, ARIH1, SDR16C5, PFN, glnA GLUL, and SRX1) were identified as the most significant (Log2 (FC) value 4) for molecular mode of action in vitro. Future in vivo studies with AMS and nanoconjugates are needed to realize the clinical potential of this work.

The effectiveness of kangaroo mother care in lowering postpartum depression in mothers of preterm and low birth weight babies: a systematic review and meta-analysis.

Background: Kangaroo mother care (KMC) intervention involves skin-to-skin contact between mother and infant. Some studies have shown a decrease in postpartum depression (PPD) in mothers of preterm and low birth weight (LBW) infants. However, the literature is scattered and of variable quality. Aims: To conduct a systematic review of available literature and provide a comprehensive picture of the effect of KMC on PPD among mothers of preterm and LBW infants. Methods: The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. After PROSPERO registration, a systematic search was conducted using PubMed, Cochrane Central Library, and Google Scholar from the inception of the databases till 14 June 2021. Of the 2944 studies assessed for titles and abstracts, nine studies with 2042 participants were included in the review. Included articles targeted mothers with LBW (<2500 g) or preterm infants (<37 weeks), used an authentic PPD tool, and had standard care or an incubator as the control group. Studies not published in English and in which mothers had a previous psychiatric illness were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized control trials and the Newcastle-Ottawa Scale for observational studies. All the results were converted to standard mean deviation and pooled together using a random-effects model with a 95% CI. A P-value of less than 0.05 is considered significant. Results: KMC Intervention was significantly associated with a lower depression score than control groups. The reduction in depression in the intervention (KMC) group was moderate: SMD=-0.38 (-0.68 to -0.08; 95% CI; I 2=86%; P=0.013). No significant difference was found between the PPD scores of both groups using the Edinburgh Postpartum Depression Scale score. Conclusions: The authors conclude that the negative effects of LBW and preterm birth experience on maternal mental health can be avoided to a moderate degree by KMC. Due to a lack of methodological uniformity, different scales for outcome measurement, and discrepancies in intervention features, significantly high heterogeneity was detected. The authors need further larger-scale studies with a uniform study design to better predict the efficacy of KMC better.

Mitigation of Benzene-Induced Haematotoxicity in Sprague Dawley Rats through Plant-Extract-Loaded Silica Nanobeads.

Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats.

Idiopathic Ileal Ulceration After Intestinal Transplantation.

Background: Idiopathic ileal ulceration after intestinal transplantation (ITx) has been discussed infrequently and has an uncertain natural history and relation to graft rejection. Herein, we review our experience with this pathology. Methods: We retrospectively reviewed 225 ITx in 217 patients with minimum 1 y graft survival. Routine graft endoscopy was conducted up to twice weekly within the first 90 d after ITx, gradually decreasing to once yearly. Risks for ulceration over time were evaluated using Cox regression. Results: Of 93 (41%) patients with ulcers, 50 were found within 90 d after ITx mostly via ileoscopy; delayed healing after biopsy appeared causal in the majority. Of the remaining 43 patients with ulcers found >90 d after ITx, 36 were after ileostomy closure. Multivariable modeling demonstrated within 90-d ulcer associations with increasing patient age (hazard ratio [HR], 1.027; P < 0.001) and loop ileostomy (versus Santulli ileostomy; HR, 0.271; P < 0.001). For ulcers appearing after ileostomy closure, their sole association was with absence of graft colon (HR, 7.232; P < 0.001). For ulcers requiring extended anti-microbial and anti-inflammatory therapy, associations included de novo donor-specific antibodies (HR, 3.222; P < 0.007) and nucleotide oligomerization domain mutations (HR, 2.772; P < 0.016). Whole-cohort post-ITx ulceration was not associated with either graft rejection (P = 0.161) or graft failure (P = 0.410). Conclusions: Idiopathic ulceration after ITx is relatively common but has little independent influence on outcome; risks include ileostomy construction, colon-free ITx, immunologic mutation, and donor sensitization.

Malabaricones from the fruit of Myristica cinnamomea King as potential agents against Acanthamoeba castellanii.

Acanthamoeba castellanii is an opportunistic free-living amoeba (FLA) pathogen which can cause fatal central nervous system (CNS) infection, granulomatous amoebic encephalitis (GAE) and potentially blinding ocular infection, Acanthamoeba keratitis (AK). Acanthamoeba species remain a challenging protist to treat due to the unavailability of safe and effective therapeutic drugs and their ability to protect themselves in the cyst stage. Natural products and their secondary metabolites play a pivotal role in drug discovery against various pathogenic microorganisms. In the present study, the ethyl acetate extract of Myristica cinnamomea King fruit was evaluated against A. castellanii (ATCC 50492), showing an IC50 of 45.102 ± 4.62 µg/mL. Previously, the bio-guided fractionation of the extract resulted in the identification of three active compounds, namely Malabaricones (A-C). The isolated and thoroughly characterized acylphenols were evaluated for their anti-amoebic activity against A. castellanii for the first time. Among tested compounds, Malabaricone B (IC50 of 101.31 ± 17.41 µM) and Malabaricone C (IC50 of 49.95 ± 6.33 µM) showed potent anti-amoebic activity against A. castellanii trophozoites and reduced their viability up-to 75 and 80 %, respectively. Moreover, both extract and Malabaricones also significantly (p < 0.05) inhibit the encystation and excystation of A. castellanii, while showed minimal toxicity against human keratinocyte cells (HaCaT cells) at lower tested concentrations. Following that, the explanation of the possible mechanism of action of purified compounds were assessed by detection of the state of chromatin. Hoechst/PI 33342 double staining showed that necrotic cell death occurred in A. castellanii trophozoites after 8 h treatment of Malabaricones (A-C). These findings demonstrate that Malabaricones B and C could serve as promising therapeutic options against A. castellanii infections.

Willingness of advanced cancer patients to receive palliative care and its determinants: A cross-sectional study in Northern Tanzania.

BACKGROUND: The purpose of this study was to assess willingness of advanced cancer patients to receive palliative care and its determinants at Cancer Care Centre in Kilimanjaro Christian Medical Centre Northern Tanzania. OBJECTIVE: The purpose of this study was to assess willingness of advanced cancer patients to receive palliative care and its determinants at Cancer Care Centre in Kilimanjaro Christian Medical Centre Northern Tanzania. METHODS: This was an institution-based cross-sectional study and the target population was all advanced cancer patients attending care at Cancer care Centre in Northern Tanzania. Data was collected using a structured questionnaire and analysed using Stata for windows 15. A descriptive analysis was conducted to summarize the data using mean standard deviation, while categorical data was summarized using frequency and percentages. Both bivariate and multivariate logistic regression analysis was used to determine the predictors associated with willingness to receive palliative care. RESULTS: The results showed that more than half of the respondents had willingness to accept palliative care. The degree of willingness PC among advanced cancer patients was high 60.6% (95%CI: 55.8-65.3). The predictors which remained significant associated with willingness to receive palliative care in multivariate analysis were the knowledgeable of palliative care [AOR: 2.86; 95%CI: 1.69-4.85] and high perceived benefits of palliative care [AOR: 3.58; 95%CI: 2.12-6.04]. CONCLUSION: Willingness to accept palliative care services was more than half of the patients just 60.6% among patients with advanced cancer from the study site. Advanced age of a patient, occupations, better knowledge, and perceived benefits for palliative care was the significant predictor for patients' willingness to accept palliative care.