Value of routine preoperative tests for coagulation before elective cranial surgery. Results of an institutional audit and a nationwide survey of neurosurgical centers in Pakistan

Background: Routine preoperative blood testing has become a dogma. The general practice is to order preoperative workup as a knee-jerk response rather than individualize it for each patient. The fact that the bleeding brain tends to swell, which coupled with limited options for proximal control, packing, and overall hemostasis, leads to an overemphasis on the preoperative coagulation profile.Material and methods: This is a retrospective review of the medical records of patients admitted at Aga Khan University Hospital from January 2010 to December 2015 for an elective craniotomy. The hospital registry was used to identify files for review. Data were collected on a predefined proforma. A nationwide survey was performed, and 30 neurosurgery centers were contacted across Pakistan to confirm the practice of preoperative workup.Results: The survey revealed that all centers had a similar practice of preoperative workup. This included complete blood count, serum electrolytes, and coagulation profile, including prothrombin time, activated partial thromboplastin time (aPTT), and international normalized ratio (INR). A total of 1800 files were reviewed. Nine (0.5%) patients were found to have deranged clotting profile without any predictive history of clotting derangement; 56% were male and 44% were female. Median age was 32 years with an interquartile range of 27 years. Median aPTT was (40.8 with 20.8 IQR). Median INR was (1.59 with 0.48 IQR). Median blood loss was (400 with 50 IQR). No significant association between coagulation profile (aPTT, INR) and blood loss was found (P = 0.85, r = -0.07).Conclusions: We conclude that patients without a history of coagulopathy and normal physical examination do not require routine coagulation screening before elective craniotomy

Drug/bioactive eluting chitosan composite foams for osteochondral tissue engineering

Joint defects associated with a variety of etiologies often extend deep into the subchondral bone leading to functional impairment and joint immobility, and it is a very challenging task to regenerate the bone-cartilage interface offering significant opportunities for biomaterial-based interventions to improve the quality of life of patients. Herein drug-/bioactive-loaded porous tissue scaffolds incorporating nano-hydroxyapatite (nHAp), chitosan (CS) and either hydroxypropyl methylcellulose (HPMC) or Bombyx mori silk fibroin (SF) are fabricated through freeze drying method as subchondral bone substitute. A combination of spectroscopy and microscopy (Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX), and X-ray fluorescence (XRF) were used to analyze the structure of the porous biomaterials. The compressive mechanical properties of these scaffolds are biomimetic of cancellous bone tissues and capable of releasing drugs/bioactives (exemplified with triamcinolone acetonide, TA, or transforming growth factor-β1, TGF-β1, respectively) over a period of days. Mouse preosteoblast MC3T3-E1 cells were observed to adhere and proliferate on the tissue scaffolds as confirmed by the cell attachment, live-dead assay and alamarBlue™ assay. Interestingly, RT-qPCR analysis showed that the TA downregulated inflammatory biomarkers and upregulated the bone-specific biomarkers, suggesting such tissue scaffolds have long-term potential for clinical application

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Electrospun Antibacterial Composites for Cartilage Tissue Engineering

Implantation of biomaterials capable of the controlled release of antibacterials during articular cartilage repair may prevent postoperative infections. Herein, biomaterials are prepared with biomimetic architectures (nonwoven mats of fibers) via electrospinning that are composed of poly(ɛ-caprolactone), poly(lactic acid), and Bombyx mori silk fibroin (with varying ratios) and, optionally, an antibiotic drug (cefixime trihydrate). The composition, morphology, and mechanical properties of the nanofibrous mats are characterized using scanning electron microscope, Fourier transform infrared spectroscopy, and tensile testing. The nonwoven mats have nanoscale fibers (typical diameters of 324–725 nm) and are capable of controlling the release profiles of the drug, with antibacterial activity against Gram +ve and Gram −ve bacteria (two common strains of human pathogenic bacteria, Staphylococcus aureus and Escherichia coli) under in vitro static conditions. The drug loaded nanofiber mats display cytocompatibility comparable to pure poly(ɛ-caprolactone) nanofibers when cultured with National Institutes of Health (NIH) NIH-3T3 fibroblast cell line and have long-term potential for clinical applications in the field of pharmaceutical sciences

Efficacy of intravenous paracetamol in combination with lidocaine pretreatment for reducing pain during injection of propofol

Introduction: The association of pain and discomfort of moderate to high severity and a high incidence with the intravenous (IV) administration of propofol is well known. Various physical and pharmacological methods are used to minimize propofol-induced pain, but the best intervention is still unknown. Therefore, our aim was to determine the analgesic efficacy of IV paracetamol when used in combination with lidocaine pretreatment in reducing propofol injection pain.Materials and methods: This double-blind, randomized controlled trial was conducted after receiving the approval of our institutional research ethics board. A total of 74 patients were included after providing informed consent, and participants were placed into two equal groups: group A received IV paracetamol (1 g) in combination with lidocaine pretreatment prior to the injection of propofol, and group B received lidocaine pretreatment alone prior to propofol injection. After propofol injection, all participants were asked to evaluate pain on the visual analog scale.Results: Patients who received the lidocaine-paracetamol combination reported significantly more pain-free responses (51.35%) than those from patients who received lidocaine pretreatment alone (8.11%; P\u3c0.05). The analgesic efficacy of group A was positive in 36 patients (97.3%), and for group B, the analgesic efficacy was positive in 24 patients (64.9%). Conclusion: The administration of IV paracetamol with lidocaine pretreatment was more effective than lidocaine pretreatment alone in reducing the pain caused by the injection of propofol. Physicians should consider using IV paracetamol in combination with lidocaine pretreatment when patients require IV propofol to ease patient suffering and reduce pain, which may help provide optimal patient care

A Quest for Livelihood Sustainability? Patterns, Motives and Determinants of Non-Farm Income Diversification among Agricultural Households in Punjab, Pakistan

Many farmers worldwide resort to choosing various income-earning options for diversifying their income sources as a means of risk-avoidance, social protection, and, above all, to finance agricultural operations. Non-farm income generation among farm families has become an imperative part of livelihood earning strategies in recent years amid fast-evolving climatic and sociodemographic changes. In this regard, this study seeks to identify the patterns and socioeconomic factors responsible for the uptake of various non-farm income diversification sources among agricultural households in southern Punjab, Pakistan. For this purpose, a total of 290 farm households were sampled using a random sampling technique to collect relevant data through structured questionnaires. Results show that approximately 79% of the surveyed farmers were involved in non-farm income generation activities, whereas, the income from these sources accounts for about 15% of total household income. The majority of the respondents offered labour for off-farm work followed by self-employment ventures. The major reason to pursue non-farm work includes low income from agriculture, mitigating risks associated with farming, and acquiring funds to finance farming operations, along with the desire to increase family income. A range of socioeconomic and infrastructure-related variables are associated with the decision to participate in specific off-farm activity, such as age, education, family size, farm income, dependency burden, farming experience, and distance to the main city. Results imply the provision of technical support to increase livelihood from farming operations to ensure food security and curb rural-urban migration. However, vocational training can enhance the rural inhabitants’ skillset to diversify on the farm through agribusiness development within rural areas, enabling them to employ local people instead of populating urban centres

Roles of Personal, Household, Physical, and Institutional Factors on Farmers’ Efficiency of Hybrid Maize Production: Implications for Food Security

This study explored the multifaceted factors influencing the efficiency of hybrid maize production and investigated the possible implications for food security. The study adopted a comprehensive approach, examining personal, household, physical, and institutional factors that affect farmers’ productivity. Findings revealed the technical, allocative, and economic efficiencies through a combination of field surveys, data analysis, and econometric modeling. The mean technical, allocative, and economic efficiency scores for the sampled farms were 0.89, 0.66, and 0.59, respectively. Moreover, the result of Tobit regression analysis showed high significance of all three efficiencies. The significant factors associated with technical efficiency were farm size, age of farm household, maize farming experience, maize farming area, distance from the farm to the main market, number of visits by extension workers, credit access, and Okara district. In addition, the number of visits by extension workers, districts (Sahiwal and Okara), age of farmers, maize farming experience, and regional disparity (Sahiwal district) had substantial influences on allocative and economic inefficiencies in the hybrid maize-growing farms. Policymakers and agricultural stakeholders can develop focused strategies to improve farmers’ productivity and overall food security by identifying the key factors associated with hybrid maize production. Tailored interventions that address knowledge gaps, improve resource allocation, and provide improved institutional support can help make food systems more sustainable and resilient