Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study.

BACKGROUND: Pakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood. METHODS: We conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019-2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6-9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent's Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child's exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables. RESULTS: A total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

Synthesis of novel nonsteroidal anti-inflammatory galloyl ß-sitosterol-loaded lignin-capped Ag-based drug.

Biocompatible anti-inflammatory lignin-capped Ag (LCAg) nanoparticles (NPs) were synthesized for the delivery of galloyl ß-sitosterol (Galloyl-BS). ß-Sitosterol (BS) is effective against inflammatory responses, like cancer-induced inflammations. BS was modified via gallic acid esterification to enhance its anti-inflammatory potential. LCAg NPs were synthesized by a green method and loaded with galloyl-BS. For comparison, pure BS was also loaded onto LCAg NPs in a separate assembly. The antioxidant potential of Galloyl-BS was greater (IC50 177 µM) than pure BS. Materials were characterized by FT-IR, SEM, XRD, and Zeta potential. Using UV-Vis spectroscopy, drug release experiments were performed by varying pH, time, concentration, and temperature. Maximum drug release was observed after 18 h at pH 6 and 40 °C. Galloyl-BS showed improved drug loading efficiency, release %age, and antioxidant activity compared to pure BS when loaded onto LCAg NPs. DLCAg exhibited excellent anti-inflammatory activity in rat models. These findings indicate that galloyl-BS (drug)-loaded LCAg (DLCAg) NPs have the potential as an anti-inflammatory agent without any prior release and scavenging in normal cells.

Silica quantum dots; an optical nanosensing approach for trace detection of pesticides in environmental and biological samples.

Both the environment and human health have suffered as a result of excessive and irrational pesticide use. The human body is vulnerable to a wide range of illnesses brought on by prolonged exposure to or intake of food contaminated with pesticide residues, including immunological and hormonal abnormalities and the development of certain tumors. Sensors based on nanoparticles stand out from more conventional spectrophotometry analytical methods due to their low detection limits, high sensitivity, and ease of use; that is why the demand for simple, fast, and less expensive sensing methods increases daily and presents myriad uses. Such demands are fulfilled by employing paper-based analytical devices having intrinsic properties. The presented work reports an on-site, easy-to-handle, and disposable paper-based sensing device for performing fast screening along with readout from a smartphone. The fabricated device utilizes luminescent silica quantum dots, immobilized into a paper cellulose matrix, and the resonance energy transfer phenomenon is employed. The silica quantum dots probes were fabricated from citric acid and, by undergoing physical adsorption, were confined on the nitrocellulose substrate in small wax-traced spots. The silica quantum dots were excited by smartphone ultraviolet LED, acting as an energy source and for capturing the image. The obtained LOD is 0.054 µM, and the coefficient of variation is less than 6.1%, comparable to the result obtained by UV-Visible and fluorometric analysis under similar experimental conditions. In addition, high reproducibility (≥9.8%) and high recovery ≥90% were obtained in spiked blood samples. The fabricated sensor sensitively detected pesticides giving a LOD of 2.5 ppm along with the development of yellow color within a short period of 5 min. The sensor functions well when sophisticated instrumentation is not accessible. The presented work shows the potential of the paper strip for the on-site detection of pesticides in biological and environmental samples.

Screening programs for common maternal mental health disorders among perinatal women: report of the systematic review of evidence.

Postpartum depression and anxiety are highly prevalent worldwide. Fisher et al., estimated the prevalence of depression and anxiety at 15.6% during the antenatal and 19.8% during the postpartum period. Their impact on maternal and child health is well-recognized among the public health community, accounting for high societal costs. The public health impact of these conditions has highlighted the need to focus on the development and provision of effective prevention and treatment strategies.In recent decades, some advances have been made in the development of effective universal and targeted screening programmes for perinatal depression and anxiety disorders. Recent research has shown potential benefits of universal and targeted screening for perinatal depression, to identify and treat undiagnosed cases, and help thwart its deleterious consequences. Ethical implications, however, for these screening programmes, without the provision of treatment have often been emphasized.The present mixed-methods systematic review and meta-analysis was conducted to collate evidence for screening programmes for perinatal depression and anxiety. It aims to answer the following questions, in a global context: For women in the perinatal period, do screening programmes for perinatal depression and anxiety compared with no screening improve maternal mental health and infant outcomes?A series of meta-analyses reveal a reduction in perinatal depression and anxiety among perinatal women undergoing screening programmes. For the outcome of depressive disorder, meta-analysis indicates a positive impact in favour of the intervention group (OR = 0.55, 95% CI: 0.45 to 0.66, n = 9009), with moderate quality of evidence. A significant improvement (high quality) was also observed in symptoms of anxiety among perinatal women (SMD = - 0.18, 95% CI: - 0.25 to - 0.12, n = 3654).

Early suspicion can save lives; mucormycosis in two children with diabetic ketoacidosis in Pakistan.

Mucormycosis is a cause of fulminant necrotising fungal infection in children with underlying immunocompromising conditions. Rhino-orbito-cerebral infection is its most common form in the paediatric group with uncontrolled diabetes mellitus or diabetic ketoacidosis. The initial presentation can mimic a bacterial infection; thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality. We have presented a case of rhino-orbito-cerebral mucormycosis (ROCM) in two patients with diabetic ketoacidosis for the first time from Pakistan. Both the patients couldnot survive due to extensive disease on late presentation.

Place & Person involved in delivery: Factors leading to delay in diagnosis of Anorectal Malformation in Newborns.

OBJECTIVE: To determine the frequency of place of delivery and person detecting the anomaly among newborn babies presenting with delayed diagnosis of anorectal malformation (ARM). METHODS: This is a Descriptive Cross-Sectional Study, conducted at Department of Paediatric Surgery, National Institute of Child Health (NICH) Karachi, from February 19, 2019 to August 18, 2019. All patients with ARM who were diagnosed beyond two hours of life (Delayed diagnosis) were included in the study. Chi square test was applied for comparison of categorical variables. RESULTS: Total 110 patients were enrolled in this study. Nineteen (17.3%) patients were delivered at home, while 91 (82.7%) were delivered at the hospital. The first person detecting the anomaly was grandmother (n=25) or a non-medical person in 58 patients (52.7%), 52 were diagnosed by a medical personal either primarily in 31 cases (28.2%) or secondarily by a neonatologist in 21 cases (19.1%). CONCLUSION: It is concluded that Non-medical person detected ARM mainly despite the babies being delivered mostly at the hospital, indicating the need for meticulous neonatal examination.

An integrated parenting intervention for maternal depression and child development in a low-resource setting: Cluster randomized controlled trial.

BACKGROUND: Rates of depression among Pakistani mothers are high, leading to poor developmental outcomes in their children. This study tested the effectiveness of a manualized integrated parenting program; Learning through Play Plus (LTP+) for maternal depression in Karachi, Pakistan. METHODS: A cluster randomized control trial conducted from January 2014 to December 2015 across 120 villages in Karachi. A total of 774 depressed mothers aged 18-44 years with children aged 0-30 months old, were included. Villages were randomized to receive LTP+ added to treatment as usual (TAU) or TAU alone. Primary outcomes were severity of maternal depression at 3 and 6 months measured by the Edinburgh Postnatal Depression Scale and child socio-emotional development at 6 months measured by the Ages and Stages Questionnaire (ASQ). Secondary outcomes included maternal anxiety, quality of life, social support, parenting competence, and knowledge about child development. RESULTS: Mothers in the LTP+ group reported significantly lower depression scores compared to those in the TAU group (6.6 vs. 13.8, effect size [ES]: -7.2; 95% confidence interval [CI]: -8.2, -6.1) at 3 and 6 months (7.2 vs. 12.00; ES: -4.6; 95% CI: -5.9, -3.4). Child socio-emotional development at 6 months was significantly better in the LTP+ group on all domains of the ASQ. There were also statistically significant improvements on all secondary outcomes at 3- and 6-month follow-up. CONCLUSION: In low-resource settings like Pakistan, low-cost integrated parenting interventions delivered by lay health workers can provide effective treatment for depressed mothers, leading to improvements in child development.

Apo-H (beta-2-glycoprotein) intact N-glycan analysis by MALDI-TOF-MS using sialic acid derivatization.

Apo-H is a plasma glycoprotein. Nearly 19% of the molecular weight of this protein is composed of glycans. Up- and down-regulation and structural changes in protein glycans provide diagnostic value for disease detection. Here, an efficient, sensitive, and optimized method is developed for Apo-H N-glycans analysis by MALDI-TOF-MS in positive mode. This bioanalytical method includes sample preparation, sample purification, and detection. An Apo-H enrichment method is developed using standard proteins by anti-Apo-H beads followed by enrichment from plasma samples. SDS-PAGE confirms the Apo-H protein enrichment, which is further verified by LC-MS/MS analysis. The lower ionization efficiency of sialylated glycan hampers their analysis by MALDI-MS. For this, stabilization of sialic acids is done by selective derivatization of carboxyl groups to differentiate between α(2,3)- and α(2,6)-linked sialic acids. Glycans are further purified by HILIC-SPE and analyzed by MALDI-MS. Several branched bi- and tri-antennary glycans with fucosylation and sialylation are identified. The reproducibility of the developed method is tested by analyzing multiple replicates of human plasma, where the same glycans are consistently identified. This method could be applied for the Apo-H glycan profiling of large clinical cohorts for diagnostic purposes.

Graphene oxide-metal oxide nanocomposites for on-target enrichment and analysis of phosphorylated biomolecules.

The surface of matrix-assisted laser desorption/ionization mass spectrometry target is modified for improved signal strength and detection of analytes. The developed method includes on-target enrichment and detection of phosphopeptides/phospholipids using graphene oxide-lanthanide metal oxides (samarium, gadolinium, dysprosium, and erbium) nanocomposites. Enriched phosphopeptides are detected using material enhanced laser desorption/ionization mass spectrometry and phospholipids by laser desorption/ionization-mass spectrometry. Nanocomposites are prepared using graphene oxide with respective metal salts at high pH. They are characterized for nano-morphology, chemistry, porosity, composition, crystallinity, and thermal stability. Phosphopeptides enrichment protocol is developed and optimized for tryptic ß-casein digest and that of phospholipids by phosphatidylcholine standard. Statistical analyses of phosphopeptides and phospholipids from milk show overlapping results for gadolinium, dysprosium, and erbium oxide nanocomposites. GO-Gd2 O3 has better enrichment efficiency and application as LDI material. Selectivity for GO-Dy2 O3 is 1:2500, for GO-Sm2 O3 is 1:3500, and 1:4000 for GO-Gd2 O3 . GO-Er2 O3 has a sensitivity of 25 fmol, whereas the highest sensitivity is down to 0.5 fmol for GO-Gd2 O3 . On-target enrichment is batch to batch reproducible with a standard deviation of <1, reduced time of enrichment to 10 min, and ease of operation compared to solid-phase batch extraction. The developed method enriches serum phosphopeptides characteristic of cancer-related phosphoproteins.

Tin derived antimony/nitrogen-doped porous carbon (Sb/NPC) composite for electrochemical sensing of albumin from hepatocellular carcinoma patients.

An electrochemical sensor based on an antimony/nitrogen-doped porous carbon (Sb/NPC) composite has been developed for the quantitative detection of albumin from hepatocellular carcinoma (HCC) patients. Sb/NPC is hydrothermally synthesized from Sn/NPC precursors. The synthesized precursor (Sn/NPC) and the product (Sb/NPC) are characterized by XRD, FTIR, TGA, UV/Vis, SEM, and AFM. Cyclic voltammetry, chronoamperometry, and electrochemical impedance studies are used to investigate the electrochemical performance of Sb/NPC-GCE. Sb/NPC-GCE detects albumin at physiological pH of 7.4 in the potential range 0.92 V and 0.09 V for oxidation and reduction, respectively. LOD and recovery of Sb/NPC-GCE for the determination of albumin are 0.13 ng.mL-1 and 66.6 ± 0.97-100 ± 2.73%, respectively. Chronoamperometry of the modified working electrode demonstrates its stability for 14 h, indicating its reusability and reproducibility. Sb/NPC-GCE is a selective sensor for albumin detection in the presence of interfering species. The electrode has been applied for albumin detection in human serum samples of HCC patients. A negative correlation of albumin with alpha-fetoprotein levels in HCC patients is observed by statistical analysis.

Iminodiacetic acid (IDA)-generated mesoporous nanopolymer: a template to relate surface area, hydrophilicity, and glycopeptides enrichment.

A three-step strategy is introduced to develop inherent iminodiacetic (IDA)-functionalized nanopolymer. SEM micrographs show homogenous spherical beads with a particle size of 500 nm. Further modification to COOH-functionalized 1,2-epoxy-5-hexene/DVB mesoporous nanopolymer enriches glycopeptides via hydrophilic interactions followed by their MS determination. Significantly high BET surface area 433.4336 m2 g-1 contributes to the improved surface hydrophilicity which is also shown by high concentration of ionizable carboxylic acids, 14.59 ± 0.25 mmol g-1. Measured surface area is the highest among DVB-based polymers and in general much higher in comparison to the previously reported BET surface areas of co-polymers, terpolymers, MOFs, and graphene-based composites. Thirty-one, 19, and 16 N-glycopeptides are enriched/identified by nanopolymer beads from tryptic digests of immunoglobulin G, horseradish peroxidase, and chicken avidin, respectively, without additional desalting steps. Material exhibits high selectivity (1:400 IgG:BSA), sensitivity (down to 0.1 fmol), regeneration ability up to three cycles, and batch-to-batch reproducibility (RSD > 1%). Furthermore, from 1 µL of digested human serum, 343 N-glycopeptide characteristics of 134 glycoproteins including 30 FDA-approved serum biomarkers are identified via nano-LC-MS/MS. The developed strategy to self-generate IDA on polymeric surface with improved surface area, porosity, and ordered morphology is insignia of its potential as chromatographic tool contributing to future developments in large-scale biomedical glycoproteomics studies.

Chlorfenapyr containing anions uptake from industrial wastewater by ethylene glycol functionalized benzyl dimethyl tetradecyl ammonium bromide membrane.

The preservation of water and wastewater treatment has become a global challenge. The concentration of anions such as chlorides, fluorides, cyanides, and perchlorates above the permitted levels in water is harmful to human and aquatic life. Chlorfenapyr is an insecticide that contains the aforesaid anions and is abundantly present in industrial wastewater. This research is focused on the removal of these anions from wastewater by ethylene glycol functionalized benzyl dimethyl tetradecyl ammonium bromide immobilized on soluble polymer anion exchange membrane. The real wastewater samples rich in chlorfenapyr from two different sources (industrial and pond) were analyzed. Membrane efficiency was more than 50 ppm for each anion in a single fold. The double folds of membrane showed enhanced uptake and separation efficiency for chloride, fluoride, and cyanide from wastewater samples between 0.01 and 0.02 ppm down to lethal concenetrations values (LD 50). The membrane shows maximum separation efficiency between the pH ranges of 6-7. The interference effect on membrane separation efficiency showed that the replacement ability of sample anions was in the order of fluoride > chloride > perchlorate > cyanide. This high replacement efficiency of fluoride and chloride is attributed to the more chemical interactions of these anions with membrane.

Enrichment of HDL proteome and phospholipidome from human serum via IMAC/MOAC affinity.

High-density lipoproteins (HDLs) have anti-inflammatory and antioxidant properties and are potentially cardio-protective. Defective HDL function is caused by alterations in both the proteome and lipidome of HDL particles. As potential biomarkers, the development of analytical methods is necessary for the enrichment of HDLs. Therefore, a method for selective enrichment of HDLs using immobilized metal ion affinity chromatography (IMAC) and metal oxide affinity chromatography (MOAC) is presented. SPE-based isolation of HDLs from whole serum is adopted as an alternative to traditional ultracentrifugation methods followed by SDS-PAGE. The enrichment mechanism relies on isoelectric points of lipoproteins and metal oxide. Negatively charged lipoprotein particles interact with positively charged metal oxides and IMAC affinity, which acts as a cation. Identified proteins from HDL through MALDI-MS analysis are apo AI, AII, AIV, CI, CIII, E, J, M, H, serum amyloid A and other nonapoproteins that are part of HDL particles and perform cellular functions. This serum-based proteomics approach gives insight into the functional role of HDL. HDL-associated phospholipids have also been analyzed by LDI-MS. Results suggest that the adopted analytical strategy is a feasible idea to extract lipoproteins from serum. A comparative study of healthy and diseased samples using this approach will provide valuable information in future.

Highly porous terpolymer-ZIF8@BA MOF composite for identification of mono- and multi-glycosylated peptides/proteins using MS-based bottom-up approach.

A hydrophilic terpolymer MOF composite is designed with high surface area and porosity to enrich mono- and multi-glycosylated peptides facilitating a bottom-up approach. Terpolymer@ZIF-8 is synthesized using free radical polymerization followed by layer by layer ZIF-8 fabrication. Subsequent surface modification was made by aminophenylboronic acid (AMBA). The enrichment ability of terpolymer@ZIF-8@BA is evaluated by using tryptic digest of IgG and HRP to exemplify mono- and multi-glycosylated protein samples. Improved selectivity of 1:200 for spiked HRP in BSA digest and sensitivity down to 1 fmol µL-1 is achieved. Batch to batch reproducibility is better 1% RSD which favors the adoption of the developed method for routine N-linked glycopeptide/protein determination. Cost-effective nature of given approach is given by regeneration of the material up to four cycles. Total 318 N-linked glycopeptides have been identified from 1 µL human serum digest after subjecting the enriched and PNGase-treated deglycosylated peptides to LC-MS. Thus, terpolymer@ZIF-8@BA holds the potential both for mono- and multi-glycosylated peptides from complex biological sample. Graphical abstract.

Magnetite nanoparticles coated with chitosan and polyethylenimine as anion exchanger for sorptive enrichment of phosphopeptides.

An anion exchange solid-phase sorbent is described. Chitosan coated magnetite nanoparticles were modified with polyethylenimine which is positively charged at pH 3 and therefore can be used for the magnet-supported enrichment of phosphopeptides which are negatively charged at this pH value. A 2-step strategy was used to synthesize the sorbent. The materials were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry and magnetic moment analysis. The anion exchanger was applied to extract phosphopeptides from a ß-casein digest. Characteristic analytical figures include (a) a loading buffer of pH 3, (b) and elution buffer of pH 11, (c) a loading time of 5 min, (d) good selectivity (the ß-casein to BSA ratio is 1:1000), and (e) excellent sensitivity (1 fmol). The optimized method was applied to egg yolk digest, non-fat milk digest, and diluted human serum. Graphical abstractSchematic representation of synthesis of PEI@chitosan@Fe3O4 nanoparticles, and of the enrichment of phosphopeptides by magnetic solid phase extraction prior to the determination of the peptides by MALDI-MS analysis.

Alumina nanocomposites: a comparative approach highlighting the improved characteristics of nanocomposites for phosphopeptides enrichment.

The work is based on the comparative study of metal oxide nanocomposites based on alumina in combination with two transition metal oxides (zirconia and titania) and two lanthanide oxides (ceria and lanthanum oxide). The choice is based on specific aims, i.e. to improve the limitations of individual metal oxides in phosphopeptide enrichment. The nanocomposites have shown improved phosphopeptide enrichment efficiency in comparison to the individual metal oxides. Alumina-zirconia show enhanced mono-phosphorylated peptide enrichment than ZrO2 whereas alumina-titania has better recovery of mono- and multi-phosphorylated peptides in comparison to individual TiO2. Alumina-ceria and alumina-lanthanum oxide overall enrich higher number of phosphopeptides. The alumina nanocomposites show higher selectivity and sensitivity for spiked ß-casein in BSA (1:1000) and diluted ß-casein digest (10 femtomole), respectively. Through the transition metal oxide nanocomposites, number of phosphoproteins from human serum are identified while this number is highest in case of alumina-lanthanum oxide nanocomposite. Thus the enrichment is affected by the choice of metal oxide in the nanocomposite based enrichment strategies.

Brief psychological intervention after self-harm: randomised controlled trial from Pakistan.

BACKGROUND: Self-harm is a major risk factor for completed suicide. AIMS: To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training (C-MAP) - delivered following an episode of self-harm compared with treatment as usual (TAU). METHOD: The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation. RESULTS: A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU. CONCLUSIONS: The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention.

Antidepressant and group psychosocial treatment for depression: a rater blind exploratory RCT from a low income country.

BACKGROUND: Research in the West shows that group psychological intervention together with an antidepressant treatment leads to more effective treatment of a depressive disorder. There are no treatment trials from low income countries comparing the efficacy of antidepressant treatment with a group psychological intervention. AIM: To conduct a feasibility trial to compare the efficacy of an antidepressant to a group psychosocial intervention, for low income women attending primary health care in Karachi, Pakistan. METHOD: This was a preliminary RCT in an urban primary health care clinic in Karachi, Pakistan. Consecutive eligible women scoring >12 on the CIS-R and >18 on Hamilton Depression Rating Scale (HDRS) (n = 66) were randomly assigned to antidepressants or a psychosocial treatment in group settings. The primary outcome measure was HDRS score; secondary outcome measures were disability and quality of life. RESULTS: More than half of the patients in both groups improved (50% reduction in HDRS scores); at end of therapy at 3 months 19 (59.4%) vs 18 (56.2%), and at 6-month follow-up 21(67.7%) vs 20(62.5%) for antidepressants and psychosocial intervention respectively. Although HDRS, BDQ and EQ5-D scores all improved considerably in both groups from start to end of treatment, and these improvements were largely maintained after a further 3 months, the differences between the two treatments were not statistically significant. CONCLUSION: Psychosocial intervention was as effective as antidepressants in reducing depression and in improving quality of life and disability at the end of therapy. However, these findings need further exploration through a larger trial.

Novel thymohydroquinone gallate derivative loaded ligand modified quantum dots as pH-sensitive multi-modal theragnostic agent for cancer treatment.

BACKGROUND: Nanomedicine, as the combination of radiopharmaceutical and nanocarrier (QDs), is developed for treating cancer. Gallic acid is antimutagenic, anti-inflammatory, and anti-carcinogenic. Typical retention time of gallic acid is approximately 4 to 8 h. To increase the retention time gallic acid is converted to prodrug by adding lipophilic moieties, encapsulating in lipophilic nanoparticles, or liposome formation. Similarly, thymoquinone is powerful antioxidant, anti-apoptotic, and anti-inflammatory effect, with reduced DNA damage. METHODS: In this study, a hydrophilic drug (gallic acid) is chemically linked to the hydrophobic drug (thymohydroquinone) to overcome the limitations of co-delivery of drugs. Thymohydroquinone (THQG) as the combination of gallic acid (GA) and thymoquinone (THQ) is loaded onto the PEI functionalized antimonene quantum dots (AM-QDs) and characterized by FTIR, UV-visible spectroscopy, X-ray powder diffraction, Zeta sizer, SEM and AFM, in-vitro and in-vivo assay, and hemolysis. RESULTS: The calculated drug loading efficiency is 90 %. Drug release study suggests the drug combination is pH sensitive and it can encounters acidic pH, releasing the drug from the nanocarrier. The drug and drug-loaded nanocarrier possesses low cytotoxicity and cell viability on MCF-7 and Cal-27 cell lines. The proposed drug delivery system is radiolabeled with Iodine-131 (131I) and Technetium (99mTc) and its deposition in various organs of rats' bodies is examined by SPECT-CT and gamma camera. Hemolytic activity of 2, 4, 6, and 8 µg/mL is 1.78, 4.16, 9.77, and 15.79 %, respectively, reflecting low levels of hemolysis. The system also sustains oxidative stress in cells and environment, decreasing ROS production to shield cells and keep them healthy. CONCLUSIONS: The results of this study suggest that the proposed drug carrier system can be used as a multi-modal theragnostic agent in cancer treatment.

Zeolite Functionalized with Magnesium/Aluminum/Lanthanum Ternary Hydroxide for the Phosphometabolite Profiling of Malignant Neoplastic Serum Samples.

ATP upregulation is a significant driver of aggressive cancer cell phenotypes. Phosphometabolites participate in metabolic pathways and are overexpressed in cancer cell activity. Therefore, developing novel and accurate methods for detecting phosphometabolites in biological fluids is essential. In this research, a novel zeolite composite comprising magnesium, aluminum, and lanthanum hydroxides (MALZ) is developed and used for the first time to enrich phosphorylated metabolites via its inherent interaction with phosphate groups. SEM micrographs show a crystalline cubic structure with a small diameter of 36.62 nm. FTIR analysis confirms the phosphate adsorption and desorption using AMP and ATP as the standards. XRD analysis of MALZ provides structural information about the synthesized composite. Adsorption-desorption parameters, such as pH, shaking time, and MALZ concentration, are optimized to analyze the binding capacity of the fabricated material for phosphorylated metabolites. A kinetic study reveals the rapid and effective AMP and ATP adsorptions on MALZ. The multiple hydroxyl groups of ternary hydroxides and high affinity of lanthanum toward the phosphate group enrich 26 phosphometabolites from serum samples of malignant neoplastic patients. The LC-MS profile shows characteristic phosphometabolites that may act as signatures of cancer-related abnormal metabolic pathways. This study may provide an experimental pathway for detecting metabolites in human body fluids.