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Patients' experiences in the intensive care unit (ICU) can enhance or impair their subsequent recovery. Improving patient and family experiences on the ICU is an important part of providing high quality care. There is little evidence to guide how to do this in a South Asian critical care context. This study addresses this gap by exploring the experiences of critically ill patients and their families in ICUs in Bangladesh and India. We elicit suggestions for improvements from patients, families and staff and highlight examples of practices that support person-centred care. This multi-site hospital ethnography was carried out in five ICUs in government hospitals in Bangladesh and India, selected using purposive sampling. Qualitative data were collected using non-participant observation and semi-structured interviews and analysed using reflexive thematic analysis. A total of 108 interviews were conducted with patients, families, and ICU staff. Over 1000 hours of observation were carried out across the five study sites. We identified important mediators of patient and family experience that span many different aspects of care. Factors that promote person-centred care include access to ICU for families, support for family involvement in care delivery, clear communication with patients and families, good symptom management for patients, support for rehabilitation, and measures to address the physical, environmental and financial needs of the family. This study has generated a list of recommendations that can be used by policy makers and practitioners who wish to implement person-centred principles in the ICU., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Inglis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sclerotinia stem rot (SSR) is a fungal disease of rapeseed/canola that causes significant seed yield losses and reduces its oil content and quality. In the present study, the reaction of 187 diverse canola genotypes to SSR was characterized at full flowering stage using the agar plug to stem inoculation method in four environments. Genome-wide association study (GWAS) using three different algorithms identified 133 significant SNPs corresponding with 123 loci for disease traits like stem lesion length (LL), lesion width (LW), and plant mortality at 14 (PM_14D) and 21 (PM_21D) days. The explained phenotypic variation of these SNPs ranged from 3.6 to 12.1%. Nineteen significant SNPs were detected in two or more environments, disease traits with at least two GWAS algorithms. The strong correlations observed between LL and other three disease traits evaluated, suggest they could be used as proxies for SSR resistance phenotyping. Sixty-nine candidate genes associated with disease resistance mechanisms were identified. Genomic prediction (GP) analysis with all the four traits employing genome-wide markers resulted in 0.41-0.64 predictive ability depending on the model specifications. The highest predictive ability for PM_21D with three models was about 0.64. From our study, the identified resistant genotypes and stable significant SNP markers will serve as a valuable resource for future SSR resistance breeding. Our study also suggests that genomic selection holds promise for accelerating canola breeding progress by enabling breeders to select SSR resistance genotypes at the early stage by reducing the need to phenotype large numbers of genotypes., (© 2021. The Author(s).)

Activities in the Bangladeshi leather industries have the potential to cause chemical pollutions thereby deteriorating the working environments, the surrounding residential areas, or even foodstuffs. Therefore, it is important to determine the chemical exposures among the industry workers and residents of the surrounding areas who may be directly or indirectly impacted by the contaminated environment. This study focused on evaluating the hazard arising from exposure to metals due to industrial contamination. Tissue samples of hair and nails were collected from both the leather industry workers and residents in the vicinity of the industries. Using chromium as an indicator of contamination/exposure from the leather industry, it was the most significant metal contaminant for industry workers ranging from 21.85 to 483 mg/kg and for industry-neighboring residents at 6.01 to 296.16 mg/kg. Both the workers and neighboring residents were found to be excessively exposed (P < 0.05) to chromium compared with the investigated control group of people living in a distant village area which had no industrial establishments.

Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability of approved targeted therapy. Therapeutic potential of immune check point inhibitors for TNBC patients is under active clinical investigation. In this study, we show that FDA-approved anti-PD-L1 antibody, atezolizumab (ATE), potentiates T cell-mediated cytotoxicity and apoptosis of TNBC cells that express higher levels of PD-L1, but does not have significant effect on TNBC cells expressing low levels of PD-L1. PD-L1 knockdown further confirmed that ability of ATE to promote T cell-induced cytotoxicity is PD-L1 expression dependent. Combination of ATE with PD-L1 upregulating agents, such as HDAC, proteasomal, and lysosomal inhibitors, further augmented cytotoxic activity of T cells toward TNBC cells. Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1 + ) TNBC, suggesting a functional association of FAK and immune checkpoints. We further demonstrate that ATE dramatically downregulates phosphorylation status of FAK, an important regulator of cell invasion and migration, and significantly enhances FAK inhibitor mediated inhibition of cell motility and invasion of PD-L1 + TNBC cells independent of T cells. Taken together, our data suggest that ATE shows promising anti-tumor activity in PD-L1 + TNBC via both T cell-dependent and -independent mechanisms.

The term "chronic Lyme disease" is used by some health care providers as a diagnosis for various constitutional, musculoskeletal, and neuropsychiatric symptoms (1,2). Patients with a diagnosis of chronic Lyme disease have been provided a wide range of medications as treatment, including long courses of intravenous (IV) antibiotics (3,4). Studies have not shown that such treatments lead to substantial long-term improvement for patients, and they can be harmful (1,5). This report describes cases of septic shock, osteomyelitis, Clostridium difficile colitis, and paraspinal abscess resulting from treatments for chronic Lyme disease. Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks.

Objectives: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population., Methods: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team., Results: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team., Conclusion: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.

Object: The objectives of this study were twofold: (1) to examine the prevalence of emotional symptoms among children and adolescents with a sports-related concussion (SRC) who were referred to a multidisciplinary pediatric concussion program and (2) to examine the prevalence, clinical features, risk factors, and management of postinjury psychiatric outcomes among those in this clinical population., Methods: The authors conducted a retrospective chart review of all patients with SRC referred to a multidisciplinary pediatric concussion program between September 2013 and October 2014. Clinical assessments carried out by a single neurosurgeon included clinical history, physical examination, and Post-Concussion Symptom Scale (PCSS) scoring. Postinjury psychiatric outcomes were defined as a subjective worsening of symptoms of a preinjury psychiatric disorder or new and isolated suicidal ideation or diagnosis of a novel psychiatric disorder (NPD). An NPD was defined as a newly diagnosed psychiatric disorder that occurred in a patient with or without a lifetime preinjury psychiatric disorder after a concussion. Clinical resources, therapeutic interventions, and clinical and return-to-play outcomes are summarized., Results: One hundred seventy-four patients (mean age 14.2 years, 61.5% male) were included in the study. At least 1 emotional symptom was reported in 49.4% of the patients, and the median emotional PCSS subscore was 4 (interquartile range 1-8) among those who reported at least 1 emotional symptom. Overall, 20 (11.5%) of the patients met the study criteria for a postinjury psychiatric outcome, including 14 patients with an NPD, 2 patients with isolated suicidal ideation, and 4 patients with worsening symptoms of a preinjury psychiatric disorder. Female sex, a higher initial PCSS score, a higher emotional PCSS subscore, presence of a preinjury psychiatric history, and presence of a family history of psychiatric illness were significantly associated with postinjury psychiatric outcomes. Interventions for patients with postinjury psychiatric outcomes included pharmacological therapy alone in 2 patients (10%), cognitive behavioral therapy alone in 4 (20%), multimodal therapy in 9 (45%), and no treatment in 5 (25%). Overall, 5 (25%) of the patients with postinjury psychiatric disorders were medically cleared to return to full sports participation, whereas 5 (25%) were lost to follow-up and 9 (45%) remained in treatment by the multidisciplinary concussion program at the end of the study period. One patient who was asymptomatic at the time of initial consultation committed suicide., Conclusions: Emotional symptoms were commonly reported among pediatric patients with SRC referred to a multidisciplinary pediatric concussion program. In some cases, these symptoms contributed to the development of an NPD, isolated suicidal ideation, and worsening symptoms of a preexisting psychiatric disorder. Future research is needed to clarify the prevalence, pathophysiology, risk factors, and evidence-based management of postinjury psychiatric outcomes after pediatric SRC. Successful management of these patients requires prompt recognition and multidisciplinary care by experts with clinical training and experience in concussion and psychiatry.

Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of chromosome 20 have been observed. Patients with supernumerary r(20) chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: Medically refractory epilepsy is amenable to neurosurgical intervention if the epileptogenic focus is accurately localized. If the scalp video-electroencephalography (EEG) and magnetic resonance imaging are nonlateralizing, yet a single focus is suspected, video-EEG monitoring with bilateral intracranial electrode placement is helpful to lateralize the ictal onset zone. We describe the indications, risks, and utility of such bilateral surveys at our institution., Methods: We retrospectively reviewed 26 patients with medically refractory seizures who were treated over a 5-year period and underwent bilateral placement of intracranial electrodes. Subdural strips were used in all cases, and additional stereotactic implantation of depth electrodes into mesial temporal lobes occurred in 50%. The mean patient age was 37.7 years, and 65.4% of patients were male., Results: The most common indication for bilateral invasive monitoring was bilateral ictal onsets on surface video-EEG (76.9%), followed by frequent interictal spikes contralateral to a single ictal focus (7.7%). Intracranial monitoring lasted an average of 8.2 days, with ictal events recorded in all cases. Ten patients (38.5%) subsequently underwent more extensive unilateral monitoring via implantation of subdural and depth electrodes through a craniotomy. A therapeutic procedure was performed in 17 patients (65.4%), whereas 1 patient underwent a palliative corpus callosotomy (3.8%). Nine patients underwent a resection without unilateral invasive mapping. Reasons for no therapeutic surgery (n = 8) included multifocal onsets, failing the Wada test, refusal of further treatment, and negative intraoperative electrocorticogram. There was 1 surgical complication, involving a retained electrode fragment that was removed in a separate minor procedure. Of the 26 patients, 15 (57.7%) are now seizure-free or have seizure disorders that have substantially improved (modified Engel classes I and II). Of the 17 patients who underwent a potentially curative surgery, 13 (76.5%) were Engel classes I and II., Conclusion: Bilateral placement of subdural strip and depth electrodes for epilepsy monitoring in patients with nonlateralizing scalp EEG and/or discordant imaging studies but clinical suspicion for focal seizure origin is both safe and effective. Given the safety and efficacy of this procedure, epileptologists should have a low threshold to consider bilateral implants for suitable patients.

Object: Depth electrodes are useful in the identification of deep epileptogenic foci. Computerized tomography-magnetic resonance (CT/MR)- and angiography-guided frame-based techniques are safe and accurate but require four-point skull fixation that limits cranial access for the placement of additional grids and strips. The authors investigated the viability and accuracy of placing depth electrodes by using a commercially available frameless system., Methods: A slotted, custom-designed adapter was built to interface with the StealthStation Guide Frame-DT and 960-525 StealthFighter. The Cranial Navigation software was used to plan the trajectory and entry site based on preoperative spoiled gradient MR imaging studies. Forty-one depth electrodes were placed in 51 targets in 20 patients. Thirty-one of these electrodes were inserted through the temporal neocortex following craniotomy and placement of subdural grids, whereas 10 were placed through burr holes. All electrodes had contact either within (71%) or touching (29%) the target, 50 of which (98%) provided adequate recordings. Although the mean distance of the distal electrode contact from the intended target was 3.1 +/- 0.5 mm, the mean distance to the edge of the anatomical structure was 0.4 +/- 0.9 mm. Placement via the laterotemporal approach was significantly (p < 0.001) more accurate than that via the occipitotemporal approach. No complication occurred., Conclusions: Depth electrodes can be placed safely and accurately by using a commercially available frameless stereotactic navigation system and a custom-made adapter. Depth electrode placement to record ictal onsets during epilepsy surgery only requires the contacts to touch rather than to reside within the intended structure. The laterotemporal approach is a more accurate method of placing electrodes than is the occipitotemporal one, likely due to the increased distance from the entry point to the target.

Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal childhood neurodegenerative lysosomal storage disease with no known therapy. There are estimated to be 200 to 300 children in the United States at any one time with the disease. LINCL is a genetic disease resulting from a deficiency of tripeptidyl peptidase I (TPP-I), a proteolytic enzyme encoded by CLN2, the gene that is mutated in individuals with LINCL. The subjects are chronically ill, with a progressive CNS disorder that invariably results in death, typically by age 8 to 12 years. The strategy of this clinical study is based on the concept that persistent expression in the CNS of the normal CLN2 cDNA with production of sufficient amounts of TPP-I should prevent further loss of neurons, and hence limit disease progression. To assess this concept, an adeno-associated virus vector (AAV2CUh-CLN2) will be used to transfer to and express the human CLN2 cDNA in the brain of children with LINCL. The vector consists of the AAV2 capsid enclosing the 4278-base single-stranded genome consisting of the two inverted terminal repeats of AAV serotype 2 and an expression cassette composed of the human cytomegalovirus (CMV) enhancer, the chicken beta-actin promoter/splice donor and 5' end of the intron, the 3' end of the rabbit P-globin intron and splice acceptor, the human CLN2 cDNA with an optimized Kozak translation initiation signal, and the polyadenylation/transcription stop codon from rabbit 3-globin. The proposed study will include 10 individuals and will be divided into two parts. Group A, to be studied first, will include four individuals with the severe form of the disease. Group B of the trial will include six individuals with a moderate form of the disease. After direct intracranial administration of the vector, there will be neurological assessment based on the LINCL clinical rating scale and magnetic resonance imaging/magnetic resonance spectroscopy assessment of the brain in regions of vector administration. The data generated will help evaluate two hypotheses: (1) that it is safe to carry out direct intracranial administration of the AAV2cuhCLN2 vector to the CNS of individuals with LINCL, and (2) that administration of the AAV2cuhCLN2 vector will slow down or halt the progression of the disease in the central nervous system.

Lennox-Gastaut syndrome is a severe age-specific epilepsy syndrome that presents with medication-resistant seizures in childhood. Antiepileptic drugs are the mainstay of treatment. Nonpharmacologic treatments include corpus callosum section and the ketogenic diet. However, no single treatment is safe and effective. We treated 13 patients with Lennox-Gastaut syndrome between the ages of 4 and 44 years (mean, 16.7 years) with vagus nerve stimulation. During the first 6 months of treatment, vagus nerve stimulation produced a median seizure rate reduction of 52% (range, 0% to 93%; P = .04). At 6 months of follow-up, three patients had a greater than 90% reduction in seizures, two had a greater than 75% reduction, one had a greater than 50% reduction, and six had at least a 25% reduction. One patient did not improve. No patient worsened after initial improvement. Side effects, including hoarseness, coughing, and pain in the throat, were transient and tolerable. No patient discontinued vagus nerve stimulation. Our results suggest that vagus nerve stimulation could be an effective and safe adjunct therapy for the treatment of Lennox-Gastaut syndrome.

Proteolytic enzymes are postulated to play a role in cell migration and synapse organization during brain development. Among these, urokinase-type plasminogen activator (uPA) has been studied in neoplastic and cultured brain cells extensively. We hypothesized that uPA, its receptor, and its inhibitors would be expressed in immature glial and neuronal cells in postnatal mouse forebrain. Immature cortical neurons were immunoreactive for uPA, its receptor, and its substrate plasminogen peaking at the end of postnatal week two, consistent with the postulated role in synaptogenesis. Immunoreactivity for uPA receptor was also observed on astroglial cells in vitro. Neither it nor uPA were convincingly detected in subventricular zone precursor cells, immature white matter or pre-labeled immature cells that had been transplanted into brain. Plasminogen activator inhibitor type 1 immunoreactivity was observed on endothelia up to 12 days age, and type 2 was observed to surround immature cells. We conclude, based on the spatial and temporal distribution of immunoreactivity, that uPA and its receptor may be relatively more important for synaptogenesis, remodeling, and reactive processes than for cell migration in developing mouse brain.

Unlabelled: The benefit of hyperbaric oxygen (HBO2) exposure is dependent on the oxygen delivery. Such benefit may be limited by the fact that hyperoxia causes vasoconstriction and decreases blood flow. The aim of this study was to determine whether regional sympathectomy attenuates this vasoconstriction response and thus improves oxygen delivery. In a double-blinded manner, healthy volunteers were subjected to HBO2 in a monoplace chamber on two occasions separated by at least 1 wk. Transcutaneous oxygen (tcPO2) and carbon dioxide (tcPCO2) on the forearm were monitored continuously, and blood flow in the axillary artery was measured using angiodynography before and after exposure to HBO2. During one visit, each volunteer received a sympathetic block to the upper extremity by an injection of lidocaine into the brachial plexus at the axilla. During a second visit, the volunteer received a placebo injection of isotonic sodium chloride solution into the brachial plexus of the same side. Skin temperature was recorded on the back of the hand. All subjects exhibited a small but significant increase in skin temperature (2.5%) and in upper limb blood flow (23%) (P < 0.05%) after sympathectomy, but not after isotonic sodium chloride solution injection. Sympathectomy increased tcPO2 marginally while in room air. However, during HBO2, tcPO2 was substantially and significantly higher (409.8+/-98.8 mm Hg) after sympathectomy compared with that after isotonic sodium chloride solution injection (171.3+/-38.1 mm Hg). tcPCO2 did not change significantly after sympathectomy or during HBO2. Thus, sympathectomy presumably improved oxygen delivery by preventing vasoconstriction during hyperoxia. The results suggest that sympathectomy may be a useful adjunct to HBO2 therapy in patients in whom vascular resistance is increased because of sympathetic tone or hyperoxia., Implications: Sympathetic nerve block of the extremities markedly enhances tissue oxygen delivery during hyperbaric oxygen treatment. Sympathectomy may be a beneficial adjunct treatment to hyperbaric oxygen in peripheral vascular insufficiency.

Interictal spikes on intraoperative electrocorticography during epilepsy are used to tailor resections. There have been a few systematic quantitative studies of anesthetic effects on these interictal discharges, and none on the effects of nitrous oxide (N2O). We calculated spike rates on ECoG on and off N2O in 18 epilepsy surgery patients with subdural strips and grids, analyzing the most active recording contract. In a blinded analyses ten patients had fewer spikes on N2O, while eight patients had more spikes on N2O. The mean spike rates did not differ (41/min on N2O and 40/min off N2O). Spike rate on and off N2O were compared using the non-parametric Wilcoxon matched pairs test. These rates were not significantly different. Our study indicates that N2O in doses employed dose not effect interictal spikes and this agent may be used during epilepsy surgery without concerns about suppression of epileptiform activity.

Of 40 patients with cortical resections for epilepsy, three had focal suppression-burst (S-B) on postresection intraoperative electrocorticography (ECoG). Eighteen to 24 months later, two patients were seizure-free and one had rare seizures. Follow-up neuropsychological testing and MRI did not reveal unexpected postoperative abnormalities. Follow-up scalp surface EEGs did not show S-B. Although S-B on postresection ECoG suggests severe localized cortical damage, this pattern near anterior temporal lobectomy resection margins was not associated with postoperative deficits.

The neuronal ceroid-lipofuscinoses (NCL), also known as Batten disease, are a not uncommon group of disorders affecting infants, children, and young adults. The abnormal ultrastructural profiles seen in NCL are used for standard diagnosis; however, they can be missed, and are also found in other neurodegenerative conditions. Furthermore, there is an overlap between the types of inclusion profiles among the different forms of NCL. Therefore, a more specific and biochemically-based marker is necessary to confirm the diagnosis of NCL. Antibodies raised against the storage material from the ovine form of NCL (mitochondrial ATP synthase subunit c) were utilized to determine whether NCL could be distinguished from other metabolic-neurodegenerative disorders. By immunoblotting and immunohistochemistry, several brain samples of well-evaluated NCL cases confirmed increased accumulations in all NCL cases except in the brain of an infantile-onset NCL patient. The immunoblot studies of skin fibroblasts and brain were sensitive but not highly specific to NCL, due to the recognition of this material in normal controls as well as in other neurogenetic diseases. Immunocytochemistry of skin fibroblasts clearly distinguished LINCL and JNCL cases from controls, and with further refinement has the potential for becoming a diagnostic tool.

Moyamoya disease is a cerebrovascular disease characterized radiologically by progressive narrowing and occlusion of the arteries contributing to the circle of Willis and its branches. There is formation of an exuberant collateral network of blood vessels at the base of the brain, which is thought to arise in response to chronic ischemia. Clinically, the course is variable, with patients having repeated transient ischemic attacks, strokes, migraine, and seizures. Effective treatment is not available. The etiology and pathophysiology of moyamoya disease are largely unknown. Two patients with arteriographically proven moyamoya disease were identified. Both patients were symptomatic before age 5 years. Despite successful encephaloduroarteriosynangiosis revascularization procedures, they continued to experience an inexorable downhill course. A calcium channel blocker (nicardipine HCl) was introduced in order to prevent further symptoms. After the introduction of nicardipine, no further strokes occurred in either patient. There were no further episodes of transient ischemic attacks, seizures, or headache in one patient and decreased frequency in the other. In patients with moyamoya disease, nicardipine may have a beneficial effect on cerebral hemodynamics and may prevent ischemic sequelae by optimizing existing collateral circulation.