Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.

Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above. Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review. Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient. Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.

Intraoperative Anesthetic Strategies to Mitigate Early Allograft Dysfunction After Orthotopic Liver Transplantation: A Narrative Review.

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

Prediction of maximum scour depth at clear water conditions: Multivariate and robust comparative analysis between empirical equations and machine learning approaches using extensive reference metadata.

Flow obstructed by bridge piers can increase sediment transport leading to local scour. This local scour poses a risk to the stability of bridge structures, which could lead to structural failures. There are two main approaches for evaluating the scour depth (ds) of bridge piers. The first is based on understanding hydraulic phenomena and developing relationships with properties affecting scour. The second uses data-driven soft computing models that lack physical interpretations but rely on algorithms to predict outcomes. Methods are chosen by researchers based on their goals and resources. This study aims to create innovative ensemble frameworks comprising support vector machine for regression (SVMR), random forest regression (RFR), and reduced error pruning tree (REPTree) as base learners, alongside bagging regression tree (BRT) and stochastic gradient boosting (SGB) as meta learners. These ensembles were developed to analyse maximum scour depths (dsm) in clear water conditions, utilizing 35 literature's experimental data published in last 63 years. The performance of each machine learning (ML) approach was assessed using statistical performance indicators. The proposed model was also compared with top six empirical equations with strong predictive ability. Results show that among these empirical equations, the equation from Nandi and Das (2023) performs best. Performance evaluation considering training, testing, and the entire dataset, SGB (REPTree), BRT(SVMR-PUK), and SGB (REPTree) exhibited the highest performance, securing the top rank among all ML models and empirical equations. Sensitivity analysis identified sediment gradation and flow intensity as the most influential variables for predicting dsm during both training and testing phases, respectively.

Neural correlates of drinking reduction during a clinical trial of cognitive behavioral therapy for alcohol use disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and goal-directed behavior, plays a role in behavior change during CBT by facilitating the regulation of craving (ROC). METHODS: Treatment-seeking participants with AUD (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning both before and after a 12-week, single-arm trial of CBT, using an ROC task that was previously shown to engage the DLPFC. RESULTS: We found that both the percentage of heavy drinking days (PHDD) and the overall self-reported alcohol craving measured during the ROC task were significantly reduced from pre- to post-CBT. However, we did not find significant changes over time in either the ability to regulate craving or regulation-related activity in any brain region. We found a significant 3-way interaction between the effects of cue-induced craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on PHDD in the left DLPFC. Follow-up analysis showed that cue-induced craving was associated with cue-induced activity in the left DLPFC among participants who ceased heavy drinking during CBT, both at pre-CBT and post-CBT timepoints. No such associations were present at either timepoint among participants who continued to drink heavily. CONCLUSIONS: These results suggest that patients in whom DLPFC functioning is more strongly related to cue-induced craving may preferentially respond to CBT.

The Road Not Taken: Disconnection of a Human-Unique Cortical Pathway Underlying Naturalistic Social Perception in Schizophrenia.

Background: Efficient processing of complex and dynamic social scenes relies on intact connectivity of many underlying cortical areas and networks, but how connectivity anomalies affect the neural substrates of social perception remains unknown. Here we measured these relationships using functionally based localization of social perception areas, resting-state functional connectivity, and movie-watching data. Methods: In 42 participants with schizophrenia (SzPs) and 41 healthy control subjects, we measured the functional connectivity of areas localized by face-emotion processing, theory-of-mind (ToM), and attention tasks. We quantified the weighted shortest path length between visual and medial prefrontal ToM areas in both populations to assess the impact of these changes in functional connectivity on network structure. We then correlated connectivity along the shortest path in each group with movie-evoked activity in a key node of the ToM network (posterior temporoparietal junction [TPJp]). Results: SzPs had pronounced decreases in connectivity in TPJ/posterior superior temporal sulcus (TPJ-pSTS) areas involved in face-emotion processing (t81 = 4.4, p = .00002). In healthy control subjects, the shortest path connecting visual and medial prefrontal ToM areas passed through TPJ-pSTS, whereas in SzPs, the shortest path passed through the prefrontal cortex. While movie-evoked TPJp activity correlated with connectivity along the TPJ-pSTS pathway in both groups (r = 0.43, p = .002), it additionally correlated with connectivity along the prefrontal cortex pathway only in SzPs (rSzP = 0.56, p = .003). Conclusions: These results suggest that connectivity along the human-unique TPJ-pSTS pathway affects both the network architecture and functioning of areas involved in processing complex dynamic social scenes. These results demonstrate how focal connectivity anomalies can have widespread impacts across the cortex.

Farmers Interpretation of Pesticides Pictograms and Their Adherence to Different Ergonomic Principles for Different Sizes.

OBJECTIVE: The objective of this study was to investigate the effect of the size of pesticide pictograms on comprehensibility and their adherence to principles of familiarity, compatibility, and standardization. Pictograms usually involve complex details, and space limitation demands size reductions, which reduces overall comprehensibility, especially in agriculture and healthcare. METHODS: Two experiments were conducted. In experiment 1, the effect of different sizes of pictograms on comprehension was tested. In experiment 2, the level of compliance for different ergonomic principles on different sizes of pictograms was investigated. RESULTS: Results of experiment 1 indicated significant variation in comprehension level (p < .05), with maximum comprehension for the size 15 mm × 15 mm (87.6%) and minimum comprehension for the size 7 mm × 7 mm (69.4%). Results of experiment 2 indicated significant variation in compliance of ergonomic principles with different pictogram sizes (p < .05), with maximum compliance for the size 15 mm × 15 mm (7.7, 7.7, 7.6) and minimum compliance for the size 7 mm × 7 mm (6.3, 6.3, 6.3). A significant increase in the comprehensibility of pictograms and their adherence to familiarity, compatibility, and standardization was observed with the increase in the sizes of pictograms. CONCLUSION: The smallest size of pictograms with a mean comprehension level ≥ 65% and scores for familiarity, compatibility, and standardization ≥ 7 (on a scale of 1 to 10) was 10 mm × 10 mm. The potential application of this research is to identify the most comprehensible size of pictograms that adhere to the principles of familiarity, compatibility, and standardization.

Use of Intramuscular Ephedrine Sulfate During Kidney Transplantation.

Hypotension during kidney transplantation can be common. Vasopressor use during these procedures is often avoided, with a fear of decreasing renal perfusion in the transplanted kidney. However, adequate perfusion for the rest of the body is also necessary, and given that these patients often have underlying hypertension or other comorbid conditions, an appropriate mean arterial pressure (MAP) has to be maintained. Intramuscular injections of ephedrine have been studied in the anesthesiology literature in a variety of case types, and it is seen as a safe and effective method to boost MAP. We present a case series of three patients who underwent renal transplantation and who received an intramuscular injection of ephedrine for hypotension control. The medication worked well for increasing blood pressures without apparent side effects. All three patients were followed for more than one year, and all patients had good graft function at the end of that time period. This series shows that while further research is necessary in this arena, intramuscular ephedrine may have a place in the management of persistent hypotension in the operating room during kidney transplantation.

Malignant Adenomyoepithelial Tumour of the Breast - a Rare Diagnosis - Case Report.

Breast adenomyoepithelioma is an unusual tumour characterized by a biphasic proliferation of epithelial and myoepithelial cells. Most of the breast adenomyoepitheliomas are considered to be benign and characterized by propensity for local recurrence. Malignant change can occur rarely in one or both cellular components. We here present a case of a 70-year-old previously healthy female who initially presented with a painless breast lump. The patient underwent wide local excision in view of suspicion of malignancy and sent for frozen section regarding the diagnosis and margins which surprisingly came as adenomyoepithelioma. Final histopathology came as low-grade malignant adenomyoepithelioma. The patient shows no sign of tumour recurrence in the follow up.

Neural correlates of drinking reduction during cognitive behavioral therapy for alcohol use disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a brain region implicated in cognitive control and goal-directed behavior, plays a role behavior change during CBT by facilitating regulation of craving. To examine this, treatment-seeking participants with AUD (N=22) underwent functional MRI scanning both before and after a 12-week single-arm trial of CBT, using a regulation of craving (ROC) fMRI task designed to measure an individual's ability to control alcohol craving and previously shown to engage the DLPFC. We found that both the number of heavy drinking days (NHDD, the primary clinical outcome) and the self-reported alcohol craving measured during the ROC paradigm were significantly reduced from pre- to post-CBT [NHDD: t=15.69, p<0.0001; alcohol craving: (F(1,21)=16.16; p=0.0006)]. Contrary to our hypothesis, there was no change in regulation effects on self-reported craving over time (F(1,21)=0.072; p=0.79), nor was there was a significant change in regulation effects over time on activity in any parcel. Searching the whole brain for neural correlates of reductions in drinking and craving after CBT, we found a significant 3-way interaction between the effects of cue-induced alcohol craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on NHDD in a parcel corresponding to area 46 of the right DLPFC (ß=-0.37, p=0.046, FDR corrected). Follow-up analyses showed that reductions in cue-induced alcohol craving from pre- to post-CBT were linearly related to reductions in alcohol cue-induced activity in area 46 only among participants who ceased heavy drinking during CBT (r=0.81, p=0.005) but not among those who continued to drink heavily (r=0.28, p=0.38). These results are consistent with a model in which CBT impacts heavy drinking by increasing the engagement of the DLPFC during cue-induced craving.

Probiotic Characterization of Indigenous Kocuria flava Y4 Strain Isolated from Dioscorea villosa Leaves.

This aim of the study was to isolate and screen potential probiotics from Dioscorea villosa leaves. The potential isolate Y4 was obtained from the Dioscorea villosa leaves, and its ability to grow in a medium containing high NaCl concentrations (2-10%) indicated its negative hemolytic activity. Furthermore, Y4 demonstrated inhibitory activity against human pathogens, such as Klebsiella pneumonia, Staphylococcus aureus, Citrobacter koseri, and Vibrio cholerae, as well as towards a plant pathogen isolate OR-2 (obtained from Citrus sinensis). Some biologically important functional groups of Y4 metabolites, such as sulfoxide; aliphatic ether; 1, 2, 3-trisubstituted, tertiary alcohol: vinyl ether; aromatic amine; carboxylic acid; nitro compound; alkene mono-substituted; and alcohol, were identified through FTIR analysis. The 16S rRNA sequencing and subsequent phylogenetic tree analysis indicated that Y4 and OR-2 are the closest neighbors to Kocuria flava (GenBank accession no. MT773277) and Pantoea dispersa (GenBank accession no. MT766308), respectively. The potential isolate Y4 was found to exhibit adhesion, auto-aggregation, co-aggregation, and weak biofilm activity. It also exhibited a high level of antimicrobial activity and antibiotic susceptibility. The safety of K. flava Y4 isolate, which is proposed to be a probiotic, was evaluated through acute oral toxicity test and biogenic amine production test. Moreover, the preservation potential of isolate Y4 was assessed through application on fruits under different temperatures. Thus, our results confirmed that Kocuria flava Y4 is a prospective probiotic and could also be used for the preservation of fruits.

Pseudoangiomatous stromal hyperplasia: A clinical perspective and a brief review.

ABSTRACT: Pseudoangiomatous stromal hyperplasia (PASH) is a benign entity of the breast and typically found incidentally or as a palpable mass. It usually affects women in the reproductive age group. In men, it is associated with gynecomastia. While the exact etiology is unknown, PASH is considered hormonally responsive. The mammography and ultrasonography findings are nonspecific. Grossly, PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slit-like spaces in dense collagenous stroma. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. PASH lesions should be surgically excised if increasing in size or associated with symptoms, also in cases of suspicious imaging findings or other lesions are synchronously diagnosed that require excision. In other small incidentally detected asymptomatic cases observation with clinicoradiological follow-up can be considered. It is associated with a good prognosis with no increased risk to develop breast cancer. Hence, the operating surgeon and pathologist should be aware of this not so uncommon entity so that patients are not subjected to unnecessary excision and subsequent physical and mental morbidity associated with it. In this article, we present a case report and also provide a brief review of the sparse literature on PASH, discussing clinical presentation, etiology and pathogenesis, radiopathological features, differential diagnosis, and the implications for further patient management and prognosis.

Hemispheric Asymmetry on the Electroencephalogram during General Anesthesia Responsive to Blood Pressure Manipulations.

The electroencephalogram (EEG) has been extensively used to detect ischemia and the need for shunting during carotid endarterectomy. Limited literature exists using EEG data to detect ischemia in other surgeries. This case report depicts a 65-year-old man, with extensive vascular history including complete left carotid occlusion and severe right carotid stenosis, who presented for left first rib resection and left subclavian vein balloon angioplasty. Following induction of general anesthesia, frontal EEG (SedLine; Masimo Corporation, Irvine, CA, USA) demonstrated hemispheric asymmetry, which nearly resolved with vasoactive support. At three distinct periods, discordance reoccurred necessitating a higher mean arterial pressure threshold. This case demonstrates EEG patterns concerning for focal spectrographic ischemia and highlights the potential use of EEG signals to capture hypoperfusion and direct vasoactive therapy.

A Case of Glycogenic Hepatopathy as a Complication of Poorly Controlled Type 1 Diabetes Mellitus.

A 23-year-old African American male with a medical history significant for poorly controlled type 1 diabetes mellitus (T1DM) presented with abdominal pain and vomiting. His laboratory workup was consistent with diabetic ketoacidosis (DKA). An acute elevation of liver enzymes was noted as the DKA resolved, with the alanine transferase and aspartate transferase levels elevated to more than 50 times the normal limit within the next 24 hours. Because abnormal liver function tests are found frequently in patients with type 1 diabetes mellitus, it is important to have a broad differential diagnosis. Furthermore, a low threshold of suspicion is required to identify a relatively underdiagnosed etiology like glycogenic hepatopathy (GH). This case report describes how patterns and trends of liver function tests provide important clues to the diagnosis of GH; how imaging modalities like ultrasonography, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) scan could be used to differentiate GH from nonalcoholic fatty liver disease (NAFLD); and how the diagnosis of GH can be made without the need for invasive liver biopsy. The knowledge about GH should prevent its delayed diagnosis and improve the outcomes by appropriately managing uncontrolled type 1 DM.

The Incidence of Alcohol Use Disorders during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has introduced a myriad of challenges to healthcare systems and public health policies across the globe. Individuals with alcohol use disorders are at peaked risk due to mental, socio-demographic, and economic factors leading to hindered mental health service access, misinformation and adherence. METHODS: Keywords including "alcohol use", "death", "hand sanitizer", "overdose" and "COVID-19" were used to obtain 8 media reports for case analysis. A review of 34 manually extracted records were also conducted using PubMed, MEDLINE, Scopus, and the Embase database with no time and language restrictions. RESULTS: A total of 2,517 individuals with alcohol overdose across the United States, India, Canada, and Iran were presented. The majority of cases were male, ages 21-65. Common contributors were linked to socio-economic changes, disruption to mental health services, and physical isolation. CONCLUSION: While original studies are essential to evaluate the etiologies of alcohol use and misuse during pandemics, the dissemination of misinformation must be curbed by directing vulnerable individuals towards accurate information and access to mental health services.

Worrisome Trends in Young-Onset Colorectal Cancer: Now Is the Time for Action.

Colorectal cancer (CRC) in the young adult population is of increasing incidence and concern. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge of CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Young-onset CRCs are characterized by more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left-colon sided location of the primary tumor. Genetic predisposition and heritable syndromes contribute to this trend, but perhaps more concerning is the majority of new diagnoses that involve no traceable genetic risk factors are sporadic. This review provides a summary of key aspects related to colorectal cancer in young adults, including epidemiology, etiology, genetics, clinical difficulties, early diagnosis, and prevention with emphasis on screening age.

Evaluation of the incidence of radial artery occlusion using different introducer sheaths and hemostasis techniques.

BACKGROUND: Radial artery occlusion (RAO) remains one of the most important complications of transradial access (TRA). Despite the identification of multiple predictors, the interaction between these predictors on the occurrence of RAO has not been evaluated. METHODS: Consecutive patients undergoing TRA coronary angiography (CA) or percutaneous coronary intervention (PCI), were retrospectively analyzed to compare the effect of standard patent hemostasis using a one-bladder band versus two-bladder band with simultaneous ipsilateral ulnar artery compression and two introducer sizes on the primary endpoint of RAO. Access was obtained using 6-Fr slender introducer sheath or 7-Fr slender introducer sheath and hemostasis with either a one-bladder band or a two-bladder band. The radial artery was evaluated using ultrasound. RESULTS: Total of 2019 patients undergoing CA or PCI were included in the analysis. In the one-bladder band group, the incidence of RAO with a 6-Fr slender introducer sheath was 4.2%. In those receiving hemostasis with a two-bladder band, RAO occurred in 1% of patients receiving a 6-Fr slender introducer sheath versus 0.9% in those receiving a 7-Fr slender introducer sheath (p = 0.68). Larger radial artery diameter, larger body weight, and a two-bladder hemostasis band with ipsilateral ulnar compression were independently associated with a lower incidence of RAO. CONCLUSION: A two-bladder band with simultaneous ipsilateral ulnar artery compression when used for radial artery hemostasis, is associated with a lower incidence of RAO, and can mitigate the penalty for a larger catheter with reassuring implications for use of a 7-Fr capable system for complex transradial PCI.

Cardiovascular Disease, Intensive Care, and Mortality in Coronavirus Disease 2019 Patients: A Meta-Analysis.

OBJECTIVE: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus-2. The coronavirus disease 2019 pandemic has imparted an extraordinary burden on the intensive care services, which is likely to echo in pandemic and critical care management glob- ally. We aim to meta-analyze mortality outcomes in cardiovascular disease patients and groups receiving corticosteroids therapy, intensive care admission status during coronavirus disease 2019 hospitalization and groups receiving corticosteroid therapy, and lastly, mortality outcomes in mechanically ventilated patients. Finally, we collate a coronavirus disease 2019 field algorithm for ST-elevation myocardial infarction critical care. METHODS: PubMed databases were searched for relevant observational studies with MeSH terms including, "cardiovascular disease," "COVID-19," "intensive care," "mortality," and "mechanical ventilation." A random-effect model was used to calculate the risk ratio, using RevMan V5.3. RESULTS: A total of 67 622 patients were included with 10 076 participants in the cardiovascular disease group. Overall, the mean age of the participants in the studies was 60 ± 1.6 years and 52.1% were female. A higher death risk was found in cardiovascular disease patients during and after coronavirus disease 2019 infection (risk ratio = 2.43, 95% CI = 1.74 to 3.41, P < .0001). Mechanical ventilation was likened to worsen mortality rates at any time during the hospital stay (risk ratio = 5.32, 95% CI = 3.89 to 7.29, P < .0001). Publication bias was not observed and high methodological qualities were included. CONCLUSIONS: Cardiovascular disease imparts a high burden on intensive care leading to high mortality among coronavirus disease 2019 patients. It is essential that myocardial infarctions in the acute care setting, and conditions such as hypertension and coronary artery diseases, are closely monitored while leading coronavirus disease 2019 hospitalization protocols.