Severe Central Nervous System and Respiratory Depression in a Neonate Following Accidental Oral Ingestion of Brimonidine Tartrate.

Brimonidine is a third-generation alpha-2 adrenergic agonist and is classified as an ocular hypotensive agent. It is used for chronic glaucoma treatment by lowering intraocular pressure, crucial for preventing blindness. Brimonidine works by reducing aqueous humor production and increasing uveoscleral outflow. The improper use of brimonidine in children can result in severe adverse effects. If brimonidine eye drops are ingested orally, it can cause significant depression of the cardiorespiratory and central nervous systems. This is a case report of a 27-day-old neonate, who presented with central nervous system and respiratory depression after accidental ingestion of one drop of brimonidine tartrate ophthalmic solution. On arrival, he was having shallow breathing, a low Glasgow Coma Scale score, pinpoint pupils, and absent deep tendon reflexes. Gastric lavage was performed and supportive treatment was started. The patient showed gradual improvement and completely recovered within 48 hours.

A Rare Case of Niemann-Pick Disease Type-A.

Niemann-Pick disease is a rare lysosomal storage, autosomal recessive disorder that impairs the body's ability to metabolize fats, thus leading to accumulation within cells. It can affect various organs, most commonly the brain, liver, spleen, bone marrow and lungs. Hepatosplenomegaly, inability to thrive and varying neurological deficits are the defining features. The three main types of Niemann-Pick disease are: NPD-A (Niemann-Pick disease type A), NPD-B (Niemann-Pick disease type B) and NPD-C (Niemann-Pick disease type C). NPD-A and NPD-B are due to enzyme acid sphingomyelinase deficiency, caused by SMPD-1 (Sphingomyelin phosphodiesterase 1) gene mutation and NPD-C is due to NPC-1 and NPC-2 (Niemann-Pick C1 and C2 protein) gene mutation. This is the case report of an 11-month-old infant who presented to OPD (Outpatient Department) with failure to thrive, abdominal distension and developmental delay. On examination the infant was emaciated, pale, had hepatosplenomegaly and developmental delay. Bone marrow and liver biopsy showed characteristic lipid-laden foamy macrophages. Thus detailed history, examination and investigations confirmed NPD-A. NPD-A has a poor prognosis and is usually fatal by three years of age. The patient was provided supportive treatment like nutritional therapy and physiotherapy, and parents were counselled regarding the disease outcome. The patient is regularly followed up, and two episodes of chest infections were reported during an 8-month period of follow-up.

Comprehensive Analysis of Salmonella Species Antibiogram and Evolving Patterns in Empirical Therapy: Insights From Tertiary Care Hospitals in Peshawar, Pakistan.

Background Typhoid fever presents a significant challenge in developing nations, exacerbated by the emergence of antibiotic-resistant strains due to widespread prevalence and overuse of antibiotics. This study seeks to assess the antibiogram profiles of Salmonella species isolated from blood cultures of patients hospitalized at two prominent tertiary care hospitals in Peshawar, Pakistan: Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC). By examining these profiles, the research aims to provide valuable insights into the evolving landscape of antibiotic resistance in the context of typhoid fever management. Materials and Methods This retrospective cross-sectional study utilized data gathered from two hospitals in Peshawar, KTH and HMC. Cases of enteric fever were identified based on positive blood cultures for Salmonella species. The study encompasses demographic information, seasonal prevalence, and antibiogram profiles of 3,137 cases that were presented between 2017 and 2023. Results Among the total 3,137 cases, males accounted for the majority, comprising 63% (2,044 cases). Particularly notable was the clustering of cases among children and adolescents aged one to 24 years. The incidence peaked during the months of summer and spring, from April to September. In terms of Salmonella Typhi isolates, considerable resistance was noted against first-line antibiotics such as amoxicillin/clavulanate (80.1%), co-trimoxazole/trimethoprim-sulfamethoxazole (66.6%), and chloramphenicol (86.9%), as well as against ceftriaxone (79.7%) and ciprofloxacin (51.6%). Conversely, certain antibiotics displayed higher sensitivity patterns, including meropenem (97.8%), doripenem (99.5%), imipenem (97.7%), ertapenem (96.5%), polymyxin B (99.4%), colistin (98.1%), and tigecycline (97.3%). Despite a limited sample size of 214 specimens, fosfomycin demonstrated a remarkable sensitivity of 93.4%. Sensitivities of amikacin and gentamicin were 90.7% and 81.5%, respectively. However, the sensitivity of azithromycin was concerning, standing at 66.5%. The antibiogram pattern for Salmonella exhibited significant and drastic changes. Conclusion In conclusion, this study sheds light on a higher prevalence of typhoid fever among males, with a notable seasonal peak observed during the summer and spring months. The age group most affected spans from one to 24 years. Salmonella isolates displayed significant resistance to conventional first-line antibiotics, alongside ciprofloxacin and third-generation cephalosporins. Azithromycin exhibited lower sensitivity compared to amikacin, gentamicin, and fosfomycin. The research advocates for the empirical use of amikacin, gentamicin, fosfomycin, and meropenem in the treatment of typhoid fever in Pakistan. Urgent measures, including regular Salmonella antibiogram surveillance, antibiotic stewardship, public health education, and Salmonella vaccination programs, are deemed crucial for primary disease prevention.

Multi-Agent Variational Approach for Robotics: A Bio-Inspired Perspective.

This study proposes an adaptable, bio-inspired optimization algorithm for Multi-Agent Space Exploration. The recommended approach combines a parameterized Aquila Optimizer, a bio-inspired technology, with deterministic Multi-Agent Exploration. Stochastic factors are integrated into the Aquila Optimizer to enhance the algorithm's efficiency. The architecture, called the Multi-Agent Exploration-Parameterized Aquila Optimizer (MAE-PAO), starts by using deterministic MAE to assess the cost and utility values of nearby cells encircling the agents. A parameterized Aquila Optimizer is then used to further increase the exploration pace. The effectiveness of the proposed MAE-PAO methodology is verified through extended simulations in various environmental conditions. The algorithm viability is further evaluated by comparing the results with those of the contemporary CME-Aquila Optimizer (CME-AO) and the Whale Optimizer. The comparison adequately considers various performance parameters, such as the percentage of the map explored, the number of unsuccessful runs, and the time needed to explore the map. The comparisons are performed on numerous maps simulating different scenarios. A detailed statistical analysis is performed to check the efficacy of the algorithm. We conclude that the proposed algorithm's average rate of exploration does not deviate much compared to contemporary algorithms. The same idea is checked for exploration time. Thus, we conclude that the results obtained for the proposed MAE-PAO algorithm provide significant advantages in terms of enhanced map exploration with lower execution times and nearly no failed runs.

Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor.

The current study focuses on molecular cloning, expression and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) from the liver of Nili-Ravi buffalo (Bubalus bubalis; Bb). RNA was isolated, genes were amplified by reverse transcriptase-polymerase chain reaction and sequence was characterized. The BbGHR sequence showed three amino acid variations in the extracellular domain when compared with Indian BbGHR. For the production of full length BbGHR and BbGHBP in Escherichia coli (E. coli) BL21 (RIPL) Codon Plus, expression plasmids were constructed under the control of T7lac promoter and isopropyl ß-D thiogalactopyranoside was used as an inducer. BbGHR and BbGHBP were expressed as inclusion bodies at ~ 40% and > 30% of the total E. coli proteins, respectively. The BbGHBP was solubilized and refolded by dilution method using cysteine-cystine redox potential. The recombinant BbGHBP was purified and biological activity was checked on HeLa cell lines showing increase cell proliferation in the presence of ovine GH (oGH), hence justifying the increase in the half-life of GH in the presence of BbGHBP. For the molecular interactions of oGH-BbGHBP multiple docking programs were employed to explore the subsequent interactions which showed high binding affinity and presence of large number of hydrogen bonds. Molecular Dynamics studies performed to examine the stability of proteins and exhibited stable structures along with favorable molecular interactions. This study has described the sequence characterization of BbGHR in Nili-Ravi buffaloes and hence provided the basis for the assessment of GH-GHR binding in other Bovidae species.

Juvenile Alexander Disease: A Rare Leukodystrophy.

Alexander disease is an uncommon autosomal dominant leukodystrophy that influences the white matter of the central nervous system (CNS), predominantly affecting the frontal lobe bilaterally. The most obvious pathogenic hallmark is the extensive deposition of cytoplasmic inclusions known as "Rosenthal fibers" in perivascular, subpial, and subependymal astrocytes throughout the CNS. The hereditary cause is mutations in the glial fibrillary acidic protein (GFAP) gene. Infantile, adult, and juvenile onsets are the three subtypes. Psychomotor retardation, mile-stone regression, spastic paresis, brain stem symptoms (swallowing, speech, etc.), and seizures define the juvenile variety, which emerges between the ages of three and 10 years. Macrocephaly has a lower likelihood of being a juvenile type. It is generally diagnosed based on clinical and magnetic resonance imaging findings. A five-year-old girl is presented as a case of juvenile Alexander disease, with typical clinical and MRI features.

Differential induction of antioxidant and anti-inflammatory phytochemicals in agitated micro-shoot cultures of Ajuga integrifolia Buch. Ham. ex D.Don with biotic elicitors.

Ajuga integrifolia Buch. Ham. ex D.Don, a member of Lamiaceae family is pharmaceutically an active perennial herb widely spread in China, Afghanistan and Pakistan Himalayan region. The application of biotic elicitors is a promising approach to cover limitations of in vitro cell technology and challenges faced by pharmaceuticals industry for bulk up production. The current study involved the induction of agitated micro-shoot cultures with the aim to investigate the growth-promoting as well as phytochemicals enhancement role of yeast extract (YE) and pectin (PE). The results showed that both elicitors induced a considerable physiological response. Biomass accumulation was observed maximum (DW: 18.3 g/L) against PE (10 mg/L) compared to YE and control. Eleven secondary phytocompounds were quantified using high-performance liquid chromatography. PE (50 mg/L) was found to be effective in elicitation of rosmarinic acid (680.20 µg/g), chlorogenic acid (294.12 µg/g), apigenin (579.61 µg/g) and quercetin (596.89 µg/g). However, maximum caffeic acid (359.52 µg/g) and luteolin (546.12 µg/g accumulation was noted in PE (1 mg/L) treatment. Harpagide, aucubin, harpagoside and 8-O-acetyl-harpagoside production was suppressed by both elicitors except for YE (100 mg/L). Catalpol accumulation in micro-shoot cultures was also downregulated except in response to YE (50 and 100 mg/L). Antioxidant activity and anti-inflammatory activity remained higher under PE (50 mg/L) and YE (100 mg/L) respectively. Therefore, results suggested that Ajuga integrifolia micro-shoot cultures treated with yeast extract and pectin might be an efficient bio-factory to produce commercially potent specific secondary metabolites.

Scarlet Flax Linum grandiflorum (L.) In Vitro Cultures as a New Source of Antioxidant and Anti-Inflammatory Lignans.

In vitro cultures of scarlet flax (Linum grandiflorum L.), an important ornamental flax, have been established as a new possible valuable resource of lignans and neolignans for antioxidant and anti-inflammatory applications. The callogenic potential at different concentrations of α-naphthalene acetic acid (NAA) and thidiazuron (TDZ), alone or in combinations, was evaluated using both L. grandiflorum hypocotyl and cotyledon explants. A higher callus induction frequency was observed on NAA than TDZ, especially for hypocotyl explants, with a maximum frequency (i.e., 95.2%) on 1.0 mg/L of NAA. The presence of NAA (1.0 mg/L) in conjunction with TDZ tended to increase the frequency of callogenesis relative to TDZ alone, but never reached the values observed with NAA alone, thereby indicating the lack of synergy between these two plant growth regulators (PGRs). Similarly, in terms of biomass, NAA was more effective than TDZ, with a maximum accumulation of biomass registered for medium supplemented with 1.0 mg/L of NAA using hypocotyls as initial explants (DW: 13.1 g). However, for biomass, a synergy between the two PGRs was observed, particularly for cotyledon-derived explants and for the lowest concentrations of TDZ. The influence of these two PGRs on callogenesis and biomass is discussed. The HPLC analysis confirmed the presence of lignans (secoisolariciresinol (SECO) and lariciresinol (LARI) and neolignan (dehydrodiconiferyl alcohol [DCA]) naturally accumulated in their glycoside forms. Furthermore, the antioxidant activities performed for both hypocotyl- and cotyledon-derived cultures were also found maximal (DPPH: 89.5%, FRAP 866: µM TEAC, ABTS: 456 µM TEAC) in hypocotyl-derived callus cultures as compared with callus obtained from cotyledon explants. Moreover, the anti-inflammatory activities revealed high inhibition (COX-1: 47.4% and COX-2: 51.1%) for extract of hypocotyl-derived callus cultures at 2.5 mg/L TDZ. The anti-inflammatory action against COX-1 and COX-2 was supported by the IC50 values. This report provides a viable approach for enhanced biomass accumulation and efficient production of (neo)lignans in L. grandiflorum callus cultures.

Interactive Effect of Light and CdO Nanoparticles on Dodonaea viscosa Morphological, Antioxidant, and Phytochemical Properties.

Cadmium nanoparticles (NPs) used in semiconducting devices are photosensitive and optically active. The objective of this study was to investigate the interactive effect of different spectral lights and CdO NPs on morphological, antioxidant, and phytochemical characteristics of Dodonaea viscosa. The plants were grown on media in the presence of green and chemically synthesized CdO NPs and under red, yellow, green, blue, and white light intensities. Results illustrated that plant morphological parameters changed in the presence of different spectral lights and NPs behaved differentially under different spectral lights. Fresh and dry weights of plants decreased in the presence of NPs in the media; however, the concentration and route of synthesis of NPs have a significant effect on these parameters. The same was observed in the case of shoot and root lengths; however, green synthesized NPs were found to be less toxic under different spectral lights. The total antixodant response increased under yellow, blue, and white lights, while the total reducing potential of plant extracts significantly varied depending upon the NP concentration and light spectrum. Different spectral lights significantly influenced the syntheses of phenolics and flavonoids under CdO NP stress and light regimes. It is concluded that toxicity of NPs also depends upon the wavelength of striking light that varies the morphological, biochemical, and antioxidative response of the plants. Furthermore, the white light might have synergistic effects of different wavelengths.

Postponement growth and antioxidative response of Brassica nigra on CuO and ZnO nanoparticles exposure under soil conditions.

Due to unique physiochemical properties, nanoparticles (NPs) have acquired substantial attention in the field of research. However, threats of ecotoxicity and phytotoxicity have limited their biological applications. In this study in vivo experiments were performed to determine the effect of CuO (12.5, 25 and 50 mg/kg) and ZnO (200, 400 and 600 mg/kg) NPs on growth, and antioxidant activities of Brassica nigra. The results showed that CuO NPs did not affect the seed germination while presence of ZnO NPs in the soil generated an inhibitory effect. Both CuO and ZnO NPs positively influenced the growth of stem and other physiological parameters i.e. stem height increased (23%) at 50 mg/kg CuO while root length decreased (up to 44%) with an increase in the concentration of NPs. Phytochemical screening of apical, middle and basal leaves showed elevated phenolic and flavonoid contents in the range of 15.3-59 µg Gallic Acid Equivalent (GAE)/mg Dry Weight (DW) and 10-35 µg Querceitin Equivalent (QE)/mg DW, respectively, in NPs-treated plants. Antioxidant activity was higher in CuO NPs-treated plants as compared to ZnO and control plants. Results conclude that CuO and ZnO NPs at low concentrations can be exploited as nanofertilisers in agriculture fields.

Green and Chemical Syntheses of CdO NPs: A Comparative Study for Yield Attributes, Biological Characteristics, and Toxicity Concerns.

Metallic nanoparticles (NPs) have enormous applications due to their remarkable physical and chemical properties. The synthesis of NPs has been a matter of concern because chemical methods are toxic. On the contrary, biological methods are considered eco-friendly. To compare the toxicity and the environment-friendly nature of the synthesis methodologies, cadmium NPs were synthesized through chemical (Ch) (co-precipitation) and biological (plant extracts as reducing agent) methods. Cadmium nitrate was reduced with NaOH, while in the biological method, the Cd ions were reduced by Artemisia scoparia (As) and Cannabis sativa (Cs) extracts. X-ray diffraction (XRD) analysis confirmed the pure single-phase cubic structure of green and chemically synthesized CdO NPs except As-CdO NPs that were crystalline cum amorphous in nature. The size of nanoparticles was 84 nm (Cs-CdO NPs) and 42.2 nm (Ch-CdO NPs). The scanning electron microscope (SEM) images exhibited an irregular disklike morphology of nanoparticles that agglomerated more in the case of green synthesis. The antioxidant and antimicrobial potential of NPs revealed that chemically synthesized NPs have better antimicrobial capability, while the antioxidative activities were better for green-synthesized NPs. However, the low yield, high ion disassociation, and waste (unreacted metal) production in the green synthesis of CdO NPs increase the risk of contamination to biosphere. Both types of NPs did not affect the seed germination of Dodonaea viscosa. However, chemically synthesized NPs were less toxic on plant morphological response. The study concludes that the chemically synthesized CdO NPs have better morphology, significant antimicrobial activity, and less toxicity to plant species compared to green-synthesized NPs. Moreover, during the green synthesis, unreacted metals are drained, which causes contamination to the ecosystem.