Clinical and neurogenetic characterisation of autosomal recessive RBL2-associated progressive neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants. To define the phenotypic effects of RBL2 mutations in detail, we identified and clinically characterized a cohort of 28 patients from 18 families carrying LOF variants in RBL2 , including fourteen new variants that substantially broaden the molecular spectrum. The clinical presentation of affected individuals is characterized by a range of neurological and developmental abnormalities. Global developmental delay and intellectual disability were uniformly observed, ranging from moderate to profound and involving lack of acquisition of key motor and speech milestones in most patients. Frequent features included postnatal microcephaly, infantile hypotonia, aggressive behaviour, stereotypic movements and non-specific dysmorphic features. Common neuroimaging features were cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. In parallel, we used the fruit fly, Drosophila melanogaster , to investigate how disruption of the conserved RBL2 orthologueue Rbf impacts nervous system function and development. We found that Drosophila Rbf LOF mutants recapitulate several features of patients harboring RBL2 variants, including alterations in the head and brain morphology reminiscent of microcephaly, and perturbed locomotor behaviour. Surprisingly, in addition to its known role in controlling tissue growth during development, we find that continued Rbf expression is also required in fully differentiated post-mitotic neurons for normal locomotion in Drosophila , and that adult-stage neuronal re-expression of Rbf is sufficient to rescue Rbf mutant locomotor defects. Taken together, this study provides a clinical and experimental basis to understand genotype-phenotype correlations in an RBL2 -linked neurodevelopmental disorder and suggests that restoring RBL2 expression through gene therapy approaches may ameliorate aspects of RBL2 LOF patient symptoms.

Abrogation of ORF8-IRF3 binding interface with Carbon nanotube derivatives to rescue the host immune system against SARS-CoV-2 by using molecular screening and simulation approaches.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to over six million deaths worldwide. In human immune system, the type 1 interferon (IFN) pathway plays a crucial role in fighting viral infections. However, the ORF8 protein of the virus evade the immune system by interacting with IRF3, hindering its nuclear translocation and consequently downregulate the type I IFN signaling pathway. To block the binding of ORF8-IRF3 and inhibit viral pathogenesis a quick discovery of an inhibitor molecule is needed. Therefore, in the present study, the interface between the ORF8 and IRF3 was targeted on a high-affinity carbon nanotube by using computational tools. After analysis of 62 carbon nanotubes by multiple docking with the induced fit model, the top five compounds with high docking scores of - 7.94 kcal/mol, - 7.92 kcal/mol, - 7.28 kcal/mol, - 7.19 kcal/mol and - 7.09 kcal/mol (top hit1-5) were found to have inhibitory activity against the ORF8-IRF3 complex. Molecular dynamics analysis of the complexes revealed the high compactness of residues, stable binding, and strong hydrogen binding network among the ORF8-nanotubes complexes. Moreover, the total binding free energy for top hit1-5 was calculated to be - 43.21 ± 0.90 kcal/mol, - 41.17 ± 0.99 kcal/mol, - 48.85 ± 0.62 kcal/mol, - 43.49 ± 0.77 kcal/mol, and - 31.18 ± 0.78 kcal/mol respectively. These results strongly suggest that the identified top five nanotubes (hit1-5) possess significant potential for advancing and exploring innovative drug therapies. This underscores their suitability for subsequent in vivo and in vitro experiments, marking them as promising candidates worthy of further investigation.

Comparison of Rapid Antigen Detection Test with Reverse Transcription Polymerase Chain Reaction in Highly Suspected COVID-19 Patients.

OBJECTIVE: To compare Rapid Antigen Test (RAT) with Reverse Transcription Polymerase Chain Reaction (RT-PCR) in highly suspected COVID-19 patients and to determine its diagnostic parameters. STUDY DESIGN: Hospital-based, descriptive/observational study. Place and Duration of the Study: Department of Medicine/COVID Complex, Medical Teaching Institution/Lady Reading Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan, from October 2021 to April 2022. METHODOLOGY: A total of 300 highly suspected cases of COVID-19 of either gender admitted in the COVID Complex of the hospital, were included. Data from the patients, including RAT and RT-PCR for COVID-19, were collected retrospectively. RT-PCR was used as the reference test and compared with RAT. Diagnostic statistics of RAT, with their respective 95% confidence intervals were calculated for RAT in diagnosing COVID-19, with significance at p ≤0.05. RESULTS: Among the 300 patients, 137 (45.7%) were males and 163 (54.3%) were females. The mean age was 56.80 ± 13.72 years. On screening, 138 (46%) patients tested positive and 162 (54%) were negative by RAT; whereas 213 (71%) tested positive and 87 (29%) were negative on RT-PCR. The sensitivity and specificity of RAT were 54.5% (95% CI: 47.52%-61.28%) and 74.7% (95% CI: 64.25%-83.42%), respectively. Positive predicted value was 84.1% (95% CI: 78.26%-88.53%) and negative predictive value was 40.1% (95% CI: 35.63%-44.79%). The positive likelihood ratio was 2.15 (95% CI: 1.47-3.15). The negative likelihood-ratio was 0.61(95% CI: 0.50-0.74). The overall accuracy was 60.33% (95% CI: 54.55%-65.91%). CONCLUSION: There was a low sensitivity and specificity of the RAT for COVID-19, with an overall accuracy of 60.33%, compared with RT-PCR. KEY WORDS: COVID-19, Rapid Antigen Test, Sensitivity, Specificity, RT-PCR.

Association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness.

Objective: To determine the association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness. Methods: A hospital-based descriptive study was conducted in the Dengue Isolation Ward of Lady Reading Hospital Peshawar from March 2020 to September 2020. Patients with Dengue fever were included in the study. The severity of the illness was categorized as "Dengue fever (DF)", "Dengue hemorrhagic fever (DHF)", and "Dengue shock syndrome (DSS)". The patients' blood groups were determined as A, B, AB, and O groups. All the data were recorded and analyzed using SPSS® version 23. Chi-square (χ2) and student t-test were applied, and a p-value of ≤0.05 was considered significant. Results: Out of 160 patients, 119(74.4%) were males; the patient's mean age was 38.09±15.68 SD, IQR=25 years. Greater proportion (28%) of the young men (up to 40 years) was affected compared to 9% young women. Fever (99%) and body aches (96%) were the most common presentation of DF, complicated by bleeding in 30.6% and shock in 9.4% of the patients. The majority (63.1%) of the patients had DF; 27.5% had DHF, and 9.4% had DSS. Sixty three (39.4%) patients had blood Group-B and 5.6% had Group-AB (p=0.97). The proportion of patients with different blood groups and the type/severity of the DF were almost identical except the fact that none of the patient with group AB had DSS. There was significant gender difference of hemoglobin (p=0.008, 95%CI=0.439, 2.844), hematocrit (p=0.012, 95%CI=0.00974, 0.07946); and Alanine Aminotransferase levels (p=0.002, 95%CI=-332.032, -72.233). Conclusion: Patients with blood Group-B were more frequent and AB was least commonly affected by the Dengue-virus infections. However, no association was found between a particular blood group and disease severity. Greater proportions of the younger men had Dengue infections.

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.

Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed the loss of a single sialic acid. Western blotting on patient-derived fibroblasts revealed reduced COG3 and COG4. Further experiments showed delayed retrograde vesicular recycling in patient cells. This report adds to the knowledge of the COG-CDG network by providing collective evidence for a COG3-CDG rare disease trait and implicating a likely pathology of the disorder as the perturbation of Golgi trafficking.

Small Cell Neuroendocrine Carcinoma of the Vagina: A Rare Presentation.

Primary small cell neuroendocrine carcinoma of the vagina is a very rare disease. We present a case study of a 52-year-old female who presented to the hospital with complaints of urinary dribbling, burning micturition, pain, and per vaginal bleeding for three to four months. A firm globular mass of approximately 5-6 cm was felt in the anterior vaginal wall per speculum examination. Diagnosis of small cell neuroendocrine carcinoma was made with tissue biopsy and immunohistochemistry. Diagnostic imaging (MRI, positron emission tomography (PET)-CT) plays a vital role in reaching the diagnosis and understanding the treatment response. The patient received six cycles of chemotherapy with cisplatin and etoposide and radiotherapy, achieving a complete response, with complete regression of the lesion. The patient had no sign of tumor recurrence and locoregional or distant metastases after six months of follow-up. Nowadays, there is no need for surgery in the treatment of vaginal small cell neuroendocrine carcinoma, rather radiotherapy and chemotherapy are the treatment of choice. We report a case of neuroendocrine cancer of the vagina treated at our institution.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'.

Structural insights into the effect of mutations in the spike protein of SARS-CoV-2 on the binding with human furin protein.

The SARS COV-2 and its variants are spreading around the world at an alarming speed, due to its higher transmissibility and the conformational changes caused by mutations. The resulting COVID-19 pandemic has imposed severe health consequences on human health. Several countries of the world including Pakistan have studied its genome extensively and provided productive findings. In the current study, the mCSM, DynaMut2, and I-Mutant servers were used to analyze the effect of identified mutations on the structural stability of spike protein however, the molecular docking and simulations approaches were used to evaluate the dynamics of the bonding network between the wild-type and mutant spike proteins with furin. We addressed the mutational modifications that have occurred in the spike protein of SARS-COV-2 that were found in 215 Pakistani's isolates of COVID-19 patients to study the influence of mutations on the stability of the protein and its interaction with the host cell. We found 7 single amino acid substitute mutations in various domains that reside in spike protein. The H49Y, N74K, G181V, and G446V were found in the S1 domain while the D614A, V622F, and Q677H mutations were found in the central helices of the spike protein. Based on the observation, G181V, G446V, D614A, and V622F mutants were found highly destabilizing and responsible for structural perturbation. Protein-protein docking and molecular simulation analysis with that of furin have predicted that all the mutants enhanced the binding efficiency however, the V622F mutant has greatly altered the binding capacity which is further verified by the KD value (7.1 E-14) and therefore may enhance the spike protein cleavage by Furin and increase the rate of infectivity by SARS-CoV-2. On the other hand, the total binding energy for each complex was calculated which revealed -50.57 kcal/mol for the wild type, for G181V -52.69 kcal/mol, for G446V -56.44 kcal/mol, for D614A -59.78 kcal/mol while for V622F the TBE was calculated to be -85.84 kcal/mol. Overall, the current finding shows that these mutations have increased the binding of Furin for spike protein and shows that D614A and V622F have significant effects on the binding and infectivity.

Progressive Multifocal Leukoencephalopathy in a Patient With Classic Hodgkin's Lymphoma Post-Bone Marrow Transplant: A Case Report.

A 29-year-old male patient underwent an autologous bone marrow transplant. He was initially diagnosed with Hodgkin's lymphoma and treated with 12 cycles of chemotherapy. Three months later, he presented with intermittent fever and underwent an MRI scan and a brain biopsy. Eventually, he was diagnosed with progressive multifocal leukoencephalopathy. For effective treatment and a plan of action, such cases necessitate multidisciplinary board meetings with input from experts in surgery, pathology, cancer, and infectious diseases.

Syntheses and structural characterization of divalent metal complexes (Co, Ni, Pd and Zn) of sterically hindered thiourea ligand and a theoretical insight of their interaction with SARS-CoV-2 enzyme.

Reacting two equivalents of sterically hindered 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with CoCl2, NiBr2, PdX2 (X = Cl; Br) and ZnI2 in acetonitrile afforded the corresponding bulky thiourea ligand stabilized four coordinated monomeric [L2CoCl2] (1), [L2NiBr2] (2), [L2PdX2] (3a: X = Cl; 3b: X = Br) and [L2ZnI2] (4.2CH3CN) complexes. Compound 1, 2 and 4.2CH3CN are tetrahedral whereas Pd complexes (3a and 3b) are square planar. In solution, palladium complexes are dominated by cis-isomers. Structural characterization shows inter- and intramolecular hydrogen bonding. Hirshfeld surface and fingerprint plots indicated significant intermolecular interactions in the crystal network. Molecular docking analysis revealed relatively higher SARS-CoV-2 enzyme interacting abilities of the synthesized complexes compared to the free ligand. All compounds have been characterized by elemental analyses, NMR spectroscopy and single-crystal X-ray diffraction.

MCNN: a multi-level CNN model for the classification of brain tumors in IoT-healthcare system.

The classification of brain tumors is significantly important for diagnosing and treating brain tumors in IoT healthcare systems. In this work, we have proposed a robust classification model for brain tumors employing deep learning techniques. In the design of the proposed method, an improved Convolutional neural network is used to classify Meningioma, Glioma, and Pituitary types of brain tumors. To test the multi-level convolutional neural network model, brain magnetic resonance image data is utilized. The MCNN model classification results were improved using data augmentation and transfer learning methods. In addition, hold-out and performance evaluation metrics have been employed in the proposed MCNN model. The experimental results show that the proposed model obtained higher outcomes than the state-of-the-art techniques and achieved 99.89% classification accuracy. Due to the higher results of the proposed approach, we recommend it for the identification of brain cancer in IoT-healthcare systems.

A Novel Nonsense Variant in GRM1 Causes Autosomal Recessive Spinocerebellar Ataxia 13 in a Consanguineous Pakistani Family.

Background and objectives: Autosomal recessive spinocerebellar ataxia-13 (SCAR13) is an ultra-rare disorder characterized by slowly progressive cerebellar ataxia, cognitive deficiencies, and skeletal and oculomotor abnormalities. The objective of this case report is to expand the clinical and molecular spectrum of SCAR13. Methods: We investigated a consanguineous Pakistani family with four patients partially presenting with clinical features of SCAR13 using whole exome sequencing. Segregation analysis was performed by Sanger sequencing in all the available individuals of the family. Results: Patients presented with quadrupedal gait, delayed developmental milestones, non-progressive peripheral neuropathy, and cognitive impairment. Whole exome sequencing identified a novel pathogenic nonsense homozygous variant, Gly240*, in the gene GRM1 as a cause of SCAR13 that segregates with the recessive disease. Discussion: We report a novel homozygous nonsense variant in the GRM1 gene in four Pakistani patients presenting with clinical features that partially overlap with the already reported phenotype of SCAR13. In addition, the family presented quadrupedal gait and non-progressive symptoms, manifestations which have not been recognized previously. So far, only four variants in GRM1 have been reported, in families of Roma, Iranian, and Tunisian origins. The current study adds to the mutation spectrum of GRM1 and provides a rare presentation of SCAR13, the first from the Pakistani population.

Gamma rays induced genetic variability in tomato (Solanum lycopersicum L.) germplasm.

The present study assessed the effectiveness of gamma radiation in inducing favorable genetic variability in tomato (Solanum lycopersicum L.). An experiment was conducted in a randomized complete block design to produce M1 generation. Significant differences were observed among the genotypes as well as between the treatments at individual plant level based on observed traits (seed germination percentage, seedling survival, plant height, number of flower clusters plant-1, number of flowers and fruits plant-1). All observed characters in the mutagenized population were adversely affected with increasing radiation dose. Results identified 450 Gy as the most damaging radiation dose followed by 300 Gy and 150 Gy. Moreover, 300 Gy treatment was identified as lethal dose (LD50) as it caused a 50% germination inhibition in almost all the evaluated genotypes. The 150 Gy treatment showed the least damaging impact and induced maximum genetic variability in almost all the genotypes under study. Character association studies were also conducted which could be utilized in the selection of desirable mutants. Correlation studies revealed an altered association among the observed parameters from positive to negative direction in 300 Gy and 450 Gy treatments as compared to control. These deviations in correlation coefficients proved that mutagenesis can break the linkage among specific loci. Furthermore, path coefficient analysis identified the growth attributes with an effective direct and indirect contribution in yield.

Whole exome sequencing identifies a novel variant causing cockayne syndrome type I in a consanguineous Pakistani family.

BACKGROUND: Cockayne syndrome (CS) is a rare neurodegenerative disorder characterized by impaired neurological functions, cachectic dwarfism, microcephaly and photosensitivity. Complementation assays identify two groups of this disorder, CS type I (CSA) and CS type II (CSB), caused by mutations in ERCC8 and ERCC6, respectively. OBJECTIVES: This study aimed to investigate the genetic basis of a consanguineous Pakistani family with three affected individuals presenting with typical clinical symptoms of CS. METHODS: We employed whole exome sequencing of the proband and then Sanger sequenced all the family members to confirm its segregation in the family. Different bioinformatics tools were used to predict pathogenicity of this variant. RESULTS: Variants were filtered according to the pedigree structure. We identified a novel homozygous variant (c.202A>T; p.Ile68Phe) in ERCC8 gene in the proband. The variant was found to segregate in the family. CONCLUSIONS: These findings add to the genetic heterogeneity of ERCC8 and expands the mutation spectrum. Also, identification of this variant can facilitate prenatal diagnosis/genetic counselling set ups in Pakistan where this disease largely remains undiagnosed.

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates.

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n-butyl (1, 3), methyl (2, 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1, 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1-4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = -3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score -5.2957). Further, the docking analysis of the HL and 1-4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2).

In Vivo Analgesic, Anti-Inflammatory, and Anti-Diabetic Screening of Bacopa monnieri-Synthesized Copper Oxide Nanoparticles.

In this work, an ecofriendly approach for biogenic production of copper oxide nanoparticles (CuO-NPs) was proposed by utilizing the Bacopa monnieri leaf extract as a reducing and stabilizing agent. The synthesis of CuO-NPs was instantly confirmed by a shift in the color of the copper solution from blue to dark gray. The use of UV-visible spectroscopy revealed a strong narrow peak at 535 nm, confirming the existence of monoclinic-shaped nanoparticles. The average size of CuO-NPs was 34.4 nm, according to scanning electron microscopy and transmission electron microscopy studies. The pristine crystalline nature of CuO-NPs was confirmed by X-ray diffraction. The monoclinic form of CuO-NPs with a crystallite size of 22 nm was determined by the sharp narrow peaks corresponding to 273, 541, 698, 684, and 366 Bragg's planes at different 2θ values. The presence of different reducing metabolites on the surface of CuO was shown by Fourier transform infrared analysis. The biological efficacy of CuO-NPs was tested against Helicobacter felis, Helicobacter suis, Helicobacter salomonis. and Helicobacter bizzozeronii. H. suis was the most susceptible strain with an inhibition zone of 15.84 ± 0.89 mm at 5 mg/mL of NPs, while the most tolerant strain was H. bizzozeronii with a 13.11 ± 0.83 mm of inhibition zone. In in vivo analgesic activity, CuO-NPs showed superior efficiency compared to controls. The maximum latency time observed was 7.14 ± 0.12 s at a dose level of 400 mg/kg after 90 min, followed by 5.21 ± 0.29 s at 400 mg/kg after 60 min, demonstrating 65 and 61% of analgesia, respectively. Diclofenac sodium was used as a standard with a latency time of 8.6 ± 0.23 s. The results observed in the rat paw edema assays showed a significant inhibitory activity of the plant-mediated CuO-NPs. The percentage inhibition of edema was 74% after 48 h for the group treated with CuO-NPs compared to the control group treated with diclofenac (100 mg/kg) with 24% edema inhibition. The solution of CuO-NPs produced 82% inhibition of edema after 21 days when compared with that of the standard drug diclofenac (73%). CuO-NPs vividly lowered glucose levels in STZ-induced diabetic mice, according to our findings. Blood glucose levels were reduced by about 33.66 and 32.19% in CuO-NP and (CuO-NP + insulin) groups of mice, respectively. From the abovementioned calculations, we can easily conclude that B. monnieri-synthesized CuO-NPs will be a potential antibacterial, anti-diabetic, and anti-inflammatory agent on in vivo and in vitro basis.

Primary Kaposiform Hemangioendothelioma of the Humerus: A Case Report.

Kaposiform hemangioendothelioma (KHE) is a neoplasm originating mainly from vessels and has a mild proclivity for malignancy. This neoplasm mainly involves somatic soft tissue and retroperitoneum. Histological findings include a nodular arrangement of oval-to-spindle cells containing pale cytoplasm. Vascular spaces are in the form of slit-like channels in which red blood cells are evident. Here, we report the case of a two-year-old male who presented with Erb's palsy and a mass lesion in the right humerus. Tissue biopsy features were compatible with KHE.

Synthesis, characterization, antioxidant, antileishmanial, anticancer, DNA and theoretical SARS-CoV-2 interaction studies of copper(II) carboxylate complexes.

Copper(II) carboxylate complexes [Cu2(OOCR)4L2] (1) and [Cu2(OOCR`)4OCO(R`)CuL2]n (2), where L = 2-methyl pyridine, R = 2-chlorophenyl acetate and R` = 2-fluorophenyl acetate were synthesized and characterized by FT-IR spectroscopy and single crystal X-ray analysis. Complex 1 exhibits the typical paddlewheel array of a dinuclear copper(II) complex with carboxylate ligands. In complex 2, this scaffold is further extended into a polymeric arrangement based on alternate paddlewheel and square planar moieties with distinct coordination spheres. The complexes showed better 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activities and have been found to be more potent antileishmanial agents than their corresponding free ligand acid species. UV-Vis absorption titrations revealed good DNA binding abilities {Kb = 9.8 × 104 M-1 (1) and 9.9 × 104 M-1 (2)} implying partial intercalation of the complexes into DNA base pairs along with groove binding. The complexes displayed in vitro cytotoxic activity against malignant glioma U-87 (MG U87) cell lines. Computational docking studies further support complex-DNA binding by intercalation. Molecular docking investigations revealed probable interactions of the complexes with spike protein, the nucleocapsid protein of SARS-CoV-2 and with the angiotensin converting enzyme of human cells.

A Case of Gastric Mucormycosis in a 21-Year-Old Patient With Hemophagocytic Lymphohistiocytosis.

Mucormycosis is an angioinvasive, opportunistic infection. Diabetes Mellitus and immunosuppression are the most common risk factors for fungal infection. Without prompt treatment, the infection can be fatal. A 21-year-old male patient presented with gastritis-like symptoms refractory to proton pump inhibitor (PPI) therapy. He recently received treatment for Hemophagocytic Lymphohistiocytosis (HLH), confirmed by bone marrow biopsy and fungal sinusitis. Esophagogastroduodenoscopy (EGD) revealed extensive gastric involvement by Mucormycosis. The patient was given antifungal drugs and a resection of necrotic stomach tissue. Gastric mucormycosis is a rare presentation of the angioinvasive fungus. The patient's young age and lack of distinguishing risk factors such as diabetes or immunosuppression are also unusual. Furthermore, the patient's unique presentation with gastric mucormycosis compounded by a recent diagnosis of Hemophagocytosis lymphohistiocytosis produces a valuable case study in management.