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Integrated Pest Management (IPM) and bio-intensive pest management (BIPM) (where Bt biopesticide is an indispensible component of it) are the suggested alternatives of chemical pesticides. So, a holistic approach to the isolation and detection of potential Bt strains, production at industrial scale and administration in the field is necessary to include Bt biopesticide in the IPM and BIPM of Bangladesh. In this connection, the bioinsecticide prepared from potential indigenous Bt strain JSc1 was applied in cabbage, cauliflower and organic tea farming and was found to be efficient in controlling the target lepidopteran pests such as Helicoverpa armigera, Spodoptera litura, Plutella xylostella, Hyposidra spp. etc. Results indicated that more than 85% of the treated crops were protected from the infestation and destruction by the pests. Obtained data analyzed using ANOVA test suggested the inclusion of Bt biopesticide in the IPM of Bangladesh as no such differences were observed with the chemical pesticides currently in use. [ABSTRACT FROM AUTHOR]

Opioid overdose is the leading cause of drug overdose lethality, posing an urgent need for investigation. The key brain region for inspiratory rhythm regulation and opioid-induced respiratory depression (OIRD) is the preBötzinger Complex (preBötC) and current knowledge has mainly been obtained from animal systems. This study aims to establish a protocol to generate human preBötC neurons from induced pluripotent cells (iPSCs) and develop an opioid overdose and recovery model utilizing these iPSC-preBötC neurons. A de novo protocol to differentiate preBötC-like neurons from human iPSCs is established. These neurons express essential preBötC markers analyzed by immunocytochemistry and demonstrate expected electrophysiological responses to preBötC modulators analyzed by patch clamp electrophysiology. The correlation of the specific biomarkers and function analysis strongly suggests a preBötC-like phenotype. Moreover, the dose-dependent inhibition of these neurons' activity is demonstrated for four different opioids with identified IC50's comparable to the literature. Inhibition is rescued by naloxone in a concentration-dependent manner. This iPSC-preBötC mimic is crucial for investigating OIRD and combating the overdose crisis and a first step for the integration of a functional overdose model into microphysiological systems., (© 2023 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Introduction: The degeneration of cortical layers is associated with cognitive decline in Alzheimer's disease (AD). Current therapies for AD are not disease-modifying, and, despite substantial efforts, research and development for AD has faced formidable challenges. In addition, cellular senescence has emerged as a significant contributor to therapy resistance., Methods: Human iPSC-derived cortical neurons were cultured on microelectrode arrays to measure long-term potentiation (LTP) noninvasively. Neurons were treated with pathogenic amyloid-β (Aβ) to analyze senescence and response to therapeutic molecules., Results: Microphysiological recordings revealed Aβ dampened cortical LTP activity and accelerated neuronal senescence. Aging neurons secreted inflammatory factors previously detected in brain, plasma, and cerebral spinal fluid of AD patients, in which drugs modulated senescence-related factors., Discussion: This platform measures and records neuronal LTP activity in response to Aβ and therapeutic molecules in real-time. Efficacy data from similar platforms have been accepted by the FDA for neurodegenerative diseases, expediting regulatory submissions., Highlights: This work developed a progerontic model of amyloid-β (Aβ)-driven cortical degeneration. This work measured neuronal LTP and correlated function with aging biomarkers. Aβ is a driver of neuronal senescence and cortical degeneration. Molecules rescued neuronal function but did not halt Aβ-driven senescence. Therapeutic molecules modulated secretion of inflammatory factors by aging neurons., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Preclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. A potential functional parameter to be monitored is long-term potentiation (LTP), which is a correlate of learning and memory, that would be one of the first functions effected by AD onset. Mature human iPSC-derived cortical neurons and primary astrocytes were co-cultured on microelectrode arrays (MEA) where surface chemistry was utilized to create circuit patterns connecting two adjacent electrodes to model LTP function. LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42 induced LTP impairment. The results presented here illustrate the significance of the system as a validated platform that can be utilized to model and study MCI AD pathology, and potentially for the pre-MCI phase before the occurrence of significant cell death. It also has the potential to become an ideal platform for high content therapeutic screening for other neurodegenerative diseases., Competing Interests: Conflict of Interest: The authors confirm that competing financial interests exist but there has been no financial support for this research that could have influenced its outcome. The only author with competing interest is J.H. who has ownership interest and is Chief Scientist and member of the Board of Directors in a company that may benefit financially as a result of the outcomes of the research or work reported in this publication.

The control of severe or chronic pain has relied heavily on opioids and opioid abuse and addiction have recently become a major global health crisis. Therefore, it is imperative to develop new pain therapeutics which have comparable efficacy for pain suppression but lack of the harmful effects of opioids. Due to the nature of pain, any in vivo experiment is undesired even in animals. Recent developments in stem cell technology has enabled the differentiation of nociceptors from human induced pluripotent stem cells. This study sought to establish an in vitro functional induced pluripotent stem cells-derived nociceptor culture system integrated with microelectrode arrays for nociceptive drug testing. Nociceptors were differentiated from induced pluripotent stem cells utilizing a modified protocol and a medium was designed to ensure prolonged and stable nociceptor culture. These neurons expressed nociceptor markers as characterized by immunocytochemistry and responded to the exogenous toxin capsaicin and the endogenous neural modulator ATP, as demonstrated with patch clamp electrophysiology. These cells were also integrated with microelectrode arrays for analgesic drug testing to demonstrate their utilization in the preclinical drug screening process. The neural activity was induced by ATP to mimic clinically relevant pathological pain and then the analgesics Lidocaine and the opioid DAMGO were tested individually and both induced immediate silencing of the nociceptive activity. This human-based functional nociceptive system provides a valuable platform for investigating pathological pain and for evaluating effective analgesics in the search of opioid substitutes., Competing Interests: MJ and JH was employed by Hesperos Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nimbalkar, Guo, Colón, Jackson, Akanda, Patel, Grillo and Hickman.)

There are many neurological rare diseases where animal models have proven inadequate or do not currently exist. NGLY1 Deficiency, a congenital disorder of deglycosylation, is a rare disease that predominantly affects motor control, especially control of neuromuscular action. In this study, NGLY1-deficient, patient-derived induced pluripotent stem cells (iPSCs) were differentiated into motoneurons (MNs) to identify disease phenotypes analogous to clinical disease pathology with significant deficits apparent in the NGLY1-deficient lines compared to the control. A neuromuscular junction (NMJ) model was developed using patient and wild type (WT) MNs to study functional differences between healthy and diseased NMJs. Reduced axon length, increased and shortened axon branches, MN action potential (AP) bursting and decreased AP firing rate and amplitude were observed in the NGLY1-deficient MNs in monoculture. When transitioned to the NMJ-coculture system, deficits in NMJ number, stability, failure rate, and synchronicity with indirect skeletal muscle (SkM) stimulation were observed. This project establishes a phenotypic NGLY1 model for investigation of possible therapeutics and investigations into mechanistic deficits in the system.

The maturation and functional characteristics of human induced pluripotent stem cell (hiPSC)-cortical neurons has not been fully documented. This study developed a phenotypic model of hiPSC-derived cortical neurons, characterized their maturation process, and investigated its application for disease modeling with the integration of multi-electrode array (MEA) technology. Immunocytochemistry analysis indicated early-stage neurons (day 21) were simultaneously positive for both excitatory (vesicular glutamate transporter 1 [VGlut1]) and inhibitory (GABA) markers, while late-stage cultures (day 40) expressed solely VGlut1, indicating a purely excitatory phenotype without containing glial cells. This maturation process was further validated utilizing patch clamp and MEA analysis. Particularly, induced long-term potentiation (LTP) successfully persisted for 1 h in day 40 cultures, but only achieved LTP in the presence of the GABA A receptor antagonist picrotoxin in day 21 cultures. This system was also applied to epilepsy modeling utilizing bicuculline and its correction utilizing the anti-epileptic drug valproic acid., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The quest to identify an effective therapeutic strategy for neurodegenerative diseases, such as mild congitive impairment (MCI) and Alzheimer's disease (AD), suffers from the lack of good human-based models. Animals represent the most common models used in basic research and drug discovery studies. However, safe and effective compounds identified in animal studies often translate poorly to humans, yielding unsuccessful clinical trials., Methods: A functional in vitro assay based on long-term potentiation (LTP) was used to demonstrate that exposure to amyloid beta (Aβ 42 ) and tau oligomers, or brain extracts from AD transgenic mice led to prominent changes in human induced pluripotent stem cells (hiPSC)-derived cortical neurons, notably, without cell death., Results: Impaired information processing was demonstrated by treatment of neuron-MEA (microelectrode array) systems with the oligomers and brain extracts by reducing the effects of LTP induction. These data confirm the neurotoxicity of molecules linked to AD pathology and indicate the utility of this human-based system to model aspects of AD in vitro and study LTP deficits without loss of viability; a phenotype that more closely models the preclinical or early stage of AD., Discussion: In this study, by combining multiple relevant and important molecular and technical aspects of neuroscience research, we generated a new, fully human in vitro system to model and study AD at the preclinical stage. This system can serve as a novel drug discovery platform to identify compounds that rescue or alleviate the initial neuronal deficits caused by Aβ 42 and/or tau oligomers, a main focus of clinical trials., Competing Interests: James J. Hickman has ownership interest and is Chief Scientist and member of the Board of Directors in a company that may benefit financially as a result of the outcomes of the research or work reported in this publication., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

There has been a tremendous amount of research into the causes of Amyotrophic Lateral Sclerosis (ALS), but yet very few treatment options beyond amelioration of symptoms. A holistic approach has shown anecdotal evidence of slowing disease progression and this treatment, known as the Deanna protocol (DP), postulates that ALS is a metabolic disease caused by glutamate that induces toxicity. In this study, glutamate exposure to human motoneurons was investigated and found not to significantly affect cell viability or electrophysiological properties. However, varicosities were observed in axons suggestive of transport impairment that was dose dependent for glutamate exposure. Surprisingly, a subset of the components of the DP eliminated these varicosities. To verify this finding a human SOD1 patient-derived iPSC line was examined and significant numbers of varicosities were present without glutamate treatment, compared to the iPSC control, indicating the possibility of a common mechanism despite different origins for the varicosities. Importantly, the DP ameliorated these varicosities by over 70% in the patient derived cells as well. These results are consistent with much of the literature on ALS and give hope for treatment not only for arresting disease progression using compounds considered safe but also the potential for restoration of function.

Muscle spindles are sensory organs embedded in the belly of skeletal muscles that serve as mechanoreceptors detecting static and dynamic information about muscle length and stretch. Through their connection with proprioceptive sensory neurons, sensation of axial body position and muscle movement are transmitted to the central nervous system. Impairment of this sensory circuit causes motor deficits and has been linked to a wide range of diseases. To date, no defined human-based in vitro model of the proprioceptive sensory circuit has been developed. The goal of this study was to develop a human-based in vitro muscle sensory circuit utilizing human stem cells. A serum-free medium was developed to drive the induction of intrafusal fibers from human satellite cells by actuation of a neuregulin signaling pathway. Both bag and chain intrafusal fibers were generated and subsequently validated by phase microscopy and immunocytochemistry. When co-cultured with proprioceptive sensory neurons derived from human neuroprogenitors, mechanosensory nerve terminal structural features with intrafusal fibers were demonstrated. Most importantly, patch-clamp electrophysiological analysis of the intrafusal fibers indicated repetitive firing of human intrafusal fibers, which has not been observed in human extrafusal fibers., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening.

Pre-clinical testing of drug candidates in animal models is expensive, time-consuming, and often fails to predict drug effects in humans. Industry and academia alike are working to build human-based in vitro test beds and advanced high throughput screening systems to improve the translation of preclinical results to human drug trials. Human neurons derived from induced pluripotent stems cells (hiPSCs) are readily available for use within these test-beds and high throughput screens, but there remains a need to robustly evaluate cellular behavior prior to their incorporation in such systems. This study reports on the characterization of one source of commercially available hiPSC-derived neurons, iCell(®) Neurons, for their long-term viability and functional performance to assess their suitability for integration within advanced in vitro platforms. The purity, morphology, survival, identity, and functional maturation of the cells utilizing different culture substrates and medium combinations were evaluated over 28 days in vitro (DIV). Patch-clamp electrophysiological data demonstrated increased capacity for repetitive firing of action potentials across all culture conditions. Significant differences in cellular maturity, morphology, and functional performance were observed in the different conditions, highlighting the importance of evaluating different surface types and growth medium compositions for application in specific in vitro protocols., (© 2015 American Institute of Chemical Engineers.)

In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.

Congenital pseudarthrosis of the tibia (CPT) is a rare malformation. It was first described by Hatzoecher in 1708. Treatment options of the congenital pseudarthrosis of tibia are variable and challenging. Various forms of bone grafts such as autologous iliac bone graft or free vascularised fibular graft, bracing, electrical stimulation, external fixators including Ilizarov technique and internal fixation with rods and plates are used. Here we represent a case of congenital pseudarthrosis of the tibia (CPT) of a 15 year-old boy, a shopkeeper hailing from Barhatta, Netrokona and diagnosed by history, clinical examination and x-ray. He was treated by Ilizarov technique and follow up was done for a period of 1 year. Complete union was achieved with correction of angulation and shortening.

The generation of an action potential (AP) is a complex process in excitable cells that involves the temporal opening and closing of several voltage-dependent ion channels within the cell membrane. The shape of an AP can carry information concerning the state of the involved ion channels as well as their relationship to cellular processes. Alteration of these ion channels by the administration of toxins, drugs, and biochemicals can change the AP's shape in a specific way, which can be characteristic for a given compound. Thus, AP shape analysis could be a valuable tool for toxin classification and the measurement of drug effects based on their mechanism of action. In an effort to begin classifying the effect of toxins on the shape of intracellularly recorded APs, patch-clamp experiments were performed on NG108-15 hybrid cells in the presence of veratridine, tetraethylammonium, and quinine. To analyze the effect, the authors generated a computer model of the AP mechanism to determine to what extent each ion channel was affected during compound administration based on the changes in the model parameters. This work is a first step toward establishing a new assay system for toxin detection and identification by AP shape analysis.

This prospective study was done to evaluate the result of interlocking intramedullary nailing in fracture shaft of the femur under the Department of Orthopaedic Surgery in Mymensingh Medical College Hospital during the period of January 2007 to December 2008. In this study total 66 patients were purposively selected for interlocking nailing initially but 6 patients did not report in subsequent follow up. So, the result of the study was based on 60 patients. There were 38 males and 22 females with the age range of 18 to 70 years, with an average age of 34 years. Motor vehicle accident was the most common cause of the fracture shaft of the femur (60%) and the second most common cause was fall from height (20%). Right sided involvement was more (66.67%). Majority of the patients had fracture lower third of the femur (70%). Among the patients farmer was the most common (33.33%) group and the next was housewife. The mean union time was 17 weeks with the range of 14 to 30 weeks. Postoperative complications were found, such as infection (3.33%) and nonunion (1.66%). The functional outcome of this study was evaluated by Klemm & Borner criteria. Excellent functional outcome was found in 80%, good in 15% and fair in 5%.

One of the earliest morphological changes occurring in apoptosis is cell shrinkage associated with an increased efflux of K(+) and Cl(-) ions. Block of K(+) or Cl(-) channels prevents cell shrinkage and death. Recently, we found evidences for the activation of a voltage-dependent anion channel in the plasma membrane (pl-VDAC) of a hippocampal cell line undergoing apoptosis. Nothing is known on pl-VDAC in apoptotic cell death of neural cells at different stages of differentiation. We have addressed this issue in primary cultures of differentiated hippocampal neurons and embryonic neural stem cells (NSCs). In control hippocampal neurons, pl-VDAC is closed but acts as an NADH-ferricyanide reductase, while in apoptotic neurons, pl-VDAC is opened and the enzymatic activity is increased. Anti-VDAC antibodies block pl-VDAC and prevent apoptosis, as well as the increase in enzymatic activity. Conversely, in NSCs, pl-VDAC is scarcely seen and there is no NADH-ferricyanide reductase activity. In agreement, anti-VDAC antibodies do not affect the apoptotic process. Instead, we find activation of a Na(+) channel that has low voltage dependency, a conductance of 26 pS, and is blocked by amiloride, which also prevents apoptosis. Thus, it appears that activation of pl-VDAC during apoptosis is a critical event in differentiated neurons, but not in NSCs.

Osteosarcoma of clavicle is extremely rare. Improved survival in patients with osteosarcomas has been associated with recent advances in imaging techniques, histopathological methods, surgery and chemotherapy. In most cases the diagnosis can be made with confidence on the x-ray appearance. Other imaging studies like- radioisotope scans may show up-skip lesions, computed tomography (CT) and magnetic resonance imaging (MRI) show the extend of the tumour. Incisional biopsy or excisional biopsy is carried out after careful clinical study and proper investigations. A 30 years old cultivator with a late case of primary osteosarcoma of clavicle was treated with pre-operative and post-operative chemotherapy and was managed with surgical excision of tumor with limb sparing. The patient was clinically disease free for about 08 (eight) months. Then the patient developed recurrences and died 11 (eleven) months after operation.

Massive or giant vesical calculus is a rare entity in the recent urological practice. Males are affected more than the females. Vesical calculi are usually secondary to bladder outlet obstruction. These patients present with recurrent urinary tract infection, haematuria or with retention of urine. We report a young male patient who presented with defaecatory problems along with other urinary symptoms. The patient having an average built, non diabetic but hypertensive. The stone could be palpated by physical examination. His urea levels were within normal limits but urine examination shows infection. USG reveals bilateral hydronephrosis with multiple stones in both kidneys along with a giant vesical calculus. After controlling urinary infection and hypertention he underwent an open cystolithotomy. During operation digital rectal help was needed to remove the stone as it was adherent with bladder mucosa. Post operative period was uneventful. His urinary output was quite normal and had no defaecatory problems. Patient left the hospital 10 days after operation.

This cross sectional and observational study was carried out among the admitted patients of the department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of 1st March 2004 to 31st March 2005. Among the all intracranial tumours, 2.5-04% are Craniopharyngiomas. Although there is a bi-modal age distribution-1st peak at 5-10 years and the 2nd peak at 55-65 years, the common patients are children (9% of childhood tumour). A typical child with Craniopharyngioma (CP) is short, obese and half blind and has a poor school record. The study has been undertaken to know in details, how child patients with Craniopharyngiomas in Bangladesh present their disease at the hospital. Earlier diagnosis and management may improve the quality of life and longivity. The average age of the patients was 13 years ranging from 07 to 17 years. The vast majority patients were admitted with visual problems as their presenting complaints. Among the patients 33% had total blindness of which 03 had primary optic atrophy and 1 has secondary optic atrophy. Among the remaining 08 patients, 75% were found to have field defect. All patients showed fundal changes ranging from early papilloedema to optic atrophy. We found major endocrinological deficiency in child patients with Craniopharyngioma in 17% cases. Raised Prolactin level may not be significant, because it could be due to stalk effect. Although 25% patients were of short stature, their hormonal profile was within normal range according to age and sex.

This cross sectional analytic study was carried out among the admitted patients of the department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of 1st July 2002 to 31st December 2004. The age ranged from 2.5 years to 70 years. The size of all posterior fossa tumors at presentation were more than 3 cm and the mean size of posterior fossa tumor was 4.38 cm. 62% of posterior fossa mid-line tumors were mixed density in NECT (non-contrast CT). Regarding enhancement characteristics, mild-moderate enhancement and marked heterogeneous enhancement was equally distributed 46% followed by marked homogeneous enhancement only 08%.. The calcification was present only in 07 (14%) patients and most of them were ependymoma. Histopathologically, medulloblastoma was the common variety (32%). The CT scan diagnostic modality sensitivity, accuracy and positive predictive value were 100%, 84.78% and 84.78% respectively but in MRI diagnostic modality 100%, 91.30% and 91.30% respectively.

Ion channels in the plasma membrane play critical roles in apoptosis. In a recent study we found that a voltage-dependent anion channel in the plasma membrane (VDACpl) of neuronal hippocampal cell line (HT22) cells was activated during apoptosis and that channel block prevented apoptosis. Whether or not VDACpl is identical to the mitochondrial VDACmt has been debated. Here, we biophysically characterize the apoptosis-inducing VDACpl and compare it with other reports of VDACpls and VDACmt. Excised membrane patches of apoptotic HT22 cells were studied with the patch-clamp technique. VDACpl has a large main-conductance state (400 pS) and occasionally subconductance states of approximately 28 pS and 220 pS. The small subconductance state is associated with long-lived inactivated states, and the large subconductance state is associated with excision of the membrane patch and subsequent activation of the channel. The open-probability curve is bell shaped with its peak around 0 mV and is blocked by 30 microM Gd3+. The gating can be described by a symmetrical seven-state model with one open state and six closed or inactivated states. These channel properties are similar to those of VDACmt and other VDACpls and are discussed in relation to apoptosis.