Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein.

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

Facile Synthesis of Barium-Doped Cadmium Sulfide Quantum Dots for the Treatment of Polluted Water: Experimental and Computational Investigations.

In this study, cadmium sulfide (CdS) quantum dots (QDs) and barium (Ba) (3 and 6 wt %)-doped CdS QDs were synthesized via a hydrothermal technique. The basic purpose of this work is to degrade methylene blue (MB) dye and evaluate density functional theory (DFT). The synthesized samples were characterized through X-ray powder diffraction (XRD), selected area electron diffraction (SAED), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), high-resolution transmission electron microscopy (HR-TEM), UV-vis spectrophotometer, PL, and density functional theory (DFT). The XRD (structural analysis) confirmed that the hexagonal crystal structure and crystallinity increased upon doping. Selected area electron diffraction (SAED) analysis confirmed the polycrystalline nature of the prepared QDs. The functional groups have been investigated using FTIR analysis. The surface and structural morphologies of the synthesized specimen have been investigated by applying TEM and FE-SEM, and it was found to exhibit the topology of QDs. In addition, optical characteristics have been investigated via UV-vis absorption spectroscopy, which exhibited a bathochromic shift (red shift) as a consequence of the reduction of the band-gap energy upon doping from 2.56 to 2.38 eV. PL analysis was used to observe the electron-hole recombination rate. Moreover, the electronic and optical properties of Ba-doped CdS were further explored using density functional theory. Pristine and Ba-doped QDs exhibit sufficient catalytic activity (CA) against the MB dye in all media as 62.59, 70.15, and 72.74% in neutral, basic, and acidic solutions, respectively.

Lhermitte-Duclos Disease: A Rare Cerebellar Hamartoma Presenting Following Traumatic Brain Injury And A Review Of The Literature.

Lhermitte-Duclos Disease (LDD) is an extremely rare hamartoma of the cerebellum and is associated with the cancer syndrome Cowden's disease. We report such a patient whose disease was diagnosed incidental to traumatic brain injury. A 40-year-old male presented after fall from stairs. CT scan revealed a large lesion in the right cerebellar hemisphere. Clinical history recounted multiple short episodes of vomiting (>10 a week) for the past 30 years and development of posterior fossa symptoms over the recent months. Neither of these had him referred due to lack of access to primary healthcare. T1 MRI with contrast showed an isointense focal mass, enhancement along the folia, and distortion of the 4th ventricle. On T2 MRI, tiger striped appearance was noted. Endoscopic third ventriculostomy was performed followed by gross total resection of the hamartoma. Histology confirmed LDD. All reported symptoms resolved following surgery. Due to lack of access to the expensive genetic testing for Cowden's he is in regular biannual follow up to be evaluated clinically for associated malignancies. We present this case to highlight the clinical-pathological characteristics of LDD, its treatment, and discuss management in the absence of genetic testing in our socio-economic demographic.

Early experience with patient-specific low-cost 3D-printed polymethylmethacrylate cranioplasty implants in a lower-middle-income-country: Technical note and economic analysis.

Background: Polymethyl methacrylate (PMMA) cranioplasty, while widely prevalent, has limitations associated with freehand manual intraoperative molding. PMMA has been superseded by titanium or Polyetheretherketone implants, prefabricated commercially from preoperative CT scans, and boasting superior clinical and cosmetic outcomes. However, such services are extremely inaccessible and unaffordable in the lower-middle-income country (LMIC) settings. The study aims to describe, in detail, the process of making ultra-low-cost patient-specific PMMA cranioplasty implants with minimum resources using open-access software. We report the first such service from the public health-care system within Pakistan, a LMIC. Methods: Using open-source software, preoperative CT heads were used to prefabricate three-dimensional implants. Both implant and cranial defects were printed using polylactic acid (PLA) to assess the implant's size and fit preoperatively. From the PLA implant, we fashioned a silicon mold that shapes the PMMA implant. Ten patients who underwent cranioplasty using our technique for various cranial defects with at least a 12-month follow-up were retrospectively reviewed. Clinical, cosmetic, and radiological outcomes were objectively assessed. Results: Etiology of injury was trauma (8), malignant MCA infarct (1), and arteriovenous fistula (1). We produced seven frontotemporal-parietal implants, one bifrontal, one frontal, and one frontoparietal. At 1 year, eight patients reported their cosmetic appearance comparable to before the defect. Radiological outcome was classified as "excellent" for eight patients. No postoperative complications were encountered, nor did any implant have to be removed. One patient's implant involving the orbital ridge had an unsatisfactory cosmetic outcome and required revision surgery. The average cost per implant to the National Health Service was US$40. Conclusion: Prefabricated patient-specific PMMA cranioplasty implants are cost-effective. A single surgeon can fashion them in a limited resource setting and provide personalized medicine with excellent clinical/cosmetic-radiological results. Our method produces patient-specific cranioplasty implants in an otherwise unaffordable LMIC setting.

Outcome of surgical treatment for neglected congenital muscular torticollis: A series of 28 adolescent patients.

Background: Congenital muscular torticollis (CMT) is a common musculoskeletal anomaly that can be excellently managed at birth with conservative physiotherapy; as a result, literature on neglected cases of CMT in older patients is sparse, and there is controversy regarding the ideal surgical approach. This report aims to provide the outcome of 28 adolescent patients with neglected CMT who underwent unipolar release at the distal sternocleidomastoid muscle (SCM). Methods: Twenty-eight adolescent patients with untreated CMT presented to our department between 2016 and 2019 and underwent unipolar release at the distal end of their SCM. All patients had no other anomaly based on clinical examination and radiological investigations. At the time of surgery, the mean age of patients was 15.8 years (range 13-18 years). There were 10 male and 18 female patients with the right side affected in 20 cases. All patients were followed up for 2 years. Patients were evaluated using an adapted version of the modified Lee's scoring system to assess cosmesis and the cervical-mandibular angle (CMA) to assess radiological change. Results: The adapted modified Lee's scoring system indicated 17 patients (60.7%) had an excellent outcome, 6 patients (21.4%) had a good outcome, and 5 patients (17.9%) had a fair outcome. In particular, scarring was fine in 23 patients (82.1%) and only slight in the remaining. Independent to the categorical outcome, all patients subjectively reported high satisfaction with their cosmesis. The preoperative mean CMA was 19.6° (range, 8.5-31.5°), which was reduced to a mean of CMA of 14.0° (range, 3-28°) after surgery (P < 0.05). No patient developed any permanent complication or required surgery for recurrence. No serious postoperative complications such as infection or hematoma were observed. Conclusion: In uncomplicated cases of neglected CMT in adolescent patients, unipolar tenotomy of the distal SCM is a safe and reliable technique with good clinical outcomes.

Usefulness of Intraoperative Computed Tomography on Extent of Resection of Large and Giant Pituitary Adenomas. Experience from a Developing Country.

BACKGROUND AND OBJECTIVE: The literature on the use of intraoperative computed tomography (iCT) is sparse. We provide our experience of the usefulness of iCT in extent of resection in large and giant pituitary adenomas. METHODS: A retrospective review was performed of cases using the endonasal endoscopic technique in which iCT was used. Demographic factors, number of scans, and impact on the extent of resection are reported, with visual acuity and field changes. Tumors were graded according to the Hardy classification. Patients with cavernous sinus invasion were excluded. RESULTS: All patients received a perioperative computed tomography scan with our iCT scanner. Thirty patients are reported, including 14 large and 16 giant pituitary adenomas, including 14 nonfunctional and 16 growth hormone-secreting tumors. The overall gross total resection (GTR), near-total resection, and subtotal resection rates were 83.3%, 16.7%, and 3.3%, respectively. iCT scanning detected residual in 13 of 30 patients, including 4 with 14 large (29%) and 9 with 16 (56.3%) giant adenomas promoting further surgery. iCT use improved GTR from 43.8% to 81.3% in giant adenomas and from 71% to 86% in large adenomas. Of the 13 patients in whom iCT detected residual disease, none required >2 iCT scans. No intraoperative complications were observed. CONCLUSIONS: iCT can improve extent of resection in large and giant pituitary adenomas and facilitate maximum safe resection such as GTR or near-total resection in patients where such should be attempted. iCT use may reduce iatrogenic complications and has select financial benefits in our patients' socioeconomic demographics. However, further prospective controlled studies are required to affirm our conclusions.

Gut microbial dysbiosis and its association with esophageal cancer.

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.

Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-L-carnitine (ALC) and metformin plus pioglitazone. METHODS: A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500 mg, 15 mg, and 1500 mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500 mg, 15 mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12 weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group. CONCLUSION: We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. TRIAL REGISTRATION: Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889 .

Therapeutic potential of medicinal plants against Leishmaniasis: a public healh concern / Potencial terapeútico de plantas medicinales contra la Leishmaniasis: un problema de salud pública

Leishmaniasis is an important disease affecting global public health which is spread by sand fly having different species. Various chemical drugs are used to treat and control Leishmaniasis including pentavalent antimonials, antimicrobial and antibiotics. Due to emergence of drug resistance, these therapeutic options are losing effectiveness in attaining success. Furthermore, these drugs are expensive and have toxic effects on liver and kidneys. There has been an emerging interest and excellent response by using plant based drugs and extracts to control Leishmaniasis. Different medicinal plants including Glycyrrhiza glabra, Allium sativum, Peganum harmala and Nigella sativa have shown excellent anti-leishmanial activity. Therefore, medicinal plants can help in effective drug development against Leishmaniasis diseases in both animals and humans which will be safer and health protective.

La Leishmaniasis es una enfermedad importante que afecta la salud pública mundial y que es transmitida por las moscas de la arena, que tienen diferentes especies. Se utilizan varios medicamentos químicos para tratar y controlar la Leishmaniasis, incluidos los antimoniales pentavalentes, antimicrobianos y antibióticos. Debido a la aparición de resistencia a los medicamentos, estas opciones terapéuticas están perdiendo eficacia para lograr el éxito. Además, estos medicamentos son costosos y tienen efectos tóxicos en hígado y riñones. Ha habido un interés emergente y una excelente respuesta mediante el uso de extractos y medicamentos a base de plantas para controlar la Leishmaniasis. Diferentes plantas medicinales como Glycyrrhiza glabra, Allium sativum, Peganum harmalay Nigella sativahan mostrado una excelente actividad anti-leishmanial. Por lo tanto, las plantas medicinales pueden ayudar en el desarrollo de fármacos eficaces contra las enfermedades de la leishmaniasis tanto en animales como en seres humanos, lo que será más seguro y proteja la salud.

Potential of botanical driven essential oils against Haemonchus contortus in small ruminants / Potencial de aceites esenciales botánicos contra Haemonchus contortus en pequeños rumiantes

The livestock sector is continuously facing problems in controlling parasitic diseases especially Haemonchosis due to emergence of anthelminthic resistance and failure in vaccination control programmes. Therefore, to increase milk and meat production and emerging demand of meat free from drug residues development of new alternative approaches are appealing for prevention and control of Haemonchosis in small ruminants. Among alternatives, plants driven essentials oils have shown promising results in control of Haemonchus contortus infection at various concentrations by different assays including egg hatch assay, larval development assay, larval exsheathment assay and adult motility assay. Essential oils are complex mixtures of various impulsive or volatile compounds which have potential to control Haemonchosis. The current study reviews the therapeutic effects of essential oils of plants against Haemonchus contortus and to be used them against Haemonchus contortus for future perspectives.

El sector ganadero enfrenta continuamente problemas para controlar las enfermedades parasitarias, especialmente la hemoncosis, debido a la aparición de resistencia antihelmíntica y al fracaso en los programas de control de vacunación. Por lo tanto, para aumentar la producción de leche y carne, y la demanda emergente de carne libre de residuos de medicamentos, el desarrollo de nuevos enfoques alternativos es atractivo para la prevención y el control de la hemoncosis en pequeños rumiantes. Entre las alternativas, los aceites esenciales producidos por las plantas han mostrado resultados prometedores en el control de la infección por Haemonchus contortus a diversas concentraciones mediante diferentes ensayos, incluido el análisis de eclosión de huevos, el desarrollo de larvas, el análisis de vaciado de larvas y el ensayo de motilidad en adultos. Los aceites esenciales son mezclas complejas de varios compuestos impulsivos o volátiles que tienen potencial para controlar la hemonchosis. Este estudio revisa los efectos terapéuticos de los aceites esenciales de las plantas contra Haemonchus contortus y evalúa sus perspectivas futuras como agentes para combatir las enfermedades causadas por este parásito.

Acaricidal and insecticidal effects of essential oils against ectoparasites of veterinary importance / Efectos acaricidas e insecticidas de los aceites esenciales contra los ectoparásitos de importancia veterinaria

Ectoparasitism in animals has become an issue of great concern that needs to be resolved to prevent huge economic losses occurring to livestock industry all over the world. Synthetic adrugs have been playing a major role in controlling ectoparasites, but their frequent and irrational use has resulted in drug resistance to routinely used chemicals and their residual effects on food and environment. Therefore, this approach of using chemical acaricides and insecticides is losing its popularity and effectiveness in controlling ectoparasites. So, the development of alternative approaches in ectoparasite management is currently required. Among alternative protocols, plants and their essential oils have played remarkable role in controlling different ectoparasites (ticks, flies, mites, lice) of veterinary importance. Essential oils have been proved to be cheaper, more effective and safer therapeautic agents against different ectoparasites of livestock importance.

En los animales el ectoparasitismo se ha convertido en un tema de gran preocupación que debe resolverse para evitar que se produzcan grandes pérdidas económicas para la industria ganadera en todo el mundo. Los aditivos sintéticos han desempeñado un papel importante en el control de los ectoparásitos, pero su uso frecuente e irracional ha dado como resultado la resistencia a los fármacos utilizados habitualmente y efectos residuales sobre los alimentos y el medio ambiente. Por lo tanto, el enfoque basado en el uso de acaricidas e insecticidas químicos está perdiendo popularidad y efectividad en el control de los ectoparásitos. Por lo tanto, actualmente se requiere el desarrollo de enfoques alternativos en el manejo de ectoparásitos. Entre los protocolos alternativos, las plantas y sus aceites esenciales han jugado un papel notable en el control de diferentes ectoparásitos (garrapatas, moscas, ácaros, piojos) de importancia veterinaria. Se ha demostrado que los aceites esenciales son agentes terapéuticos más baratos, más efectivos y más seguros contra diferentes ectoparásitos de importancia ganadera.