Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.

Clinical characteristics and outcomes of nosocomial COVID-19 in Turkey:A retrospective multicenter study

Objective:To identify the clinical characteristics and outcomes of hospital-acquired SARS-CoV-2 infection during the vaccination period nationwide in Turkey.Methods:COVID-19 patients followed in the pandemic services across Turkey between January 1,2021,and March 31,2022 were investigated retrospectively.Nosocomial COVID-19 was defined as a patient neither diagnosed with COVID-19 nor suspected COVID-19 at the hospital admission and was confirmed COVID-19≥5 days after hospital admission.The primary outcome of this study was in-hospital mortality;demographic features and vaccination status was compared between survivors and non-survivors.Results:During the study period,15573 COVID-19 patients were followed in 18 centers and 543(3.5%)patients were nosocomial COVID-19.Most patients with nosocomial COVID-19(80.4%)were transferred from medical wards.162(29.8%)of the patients with nosocomial COVID-19 admitted to the intensive care unit due to disease severity and 138(25.4%)of the patients died during hospital stay.Advanced age(≥65 years)and number of comorbid diseases(≥2)was found to be associated with mortality in nosocomial COVID-19(OR 1.74,95%CI 1.11-2.74 and OR 1.60,95%CI 1.02-2.56,respectively).Vaccination was associated with survival in nosocomial COVID-19(OR 0.25,95%CI 0.16-0.38).Conclusions:Patients with nosocomial COVID-19 had increased admission to intensive care units and higher mortality rate.Vaccination can decrease the in-hospital mortality rate.

Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional impairment.Stem cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain.Wharton’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological deficits.AIM To evaluate the safety and efficiency of MSC therapy in TBI.METHODS We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a TBI.These 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application route.Spasticity was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical Research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status scale.RESULTS Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to i.m.injection,which resolved within 24 h.During the one year follow-up,no other safety issues or adverse events were reported.These 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the intervention.MAS values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest analyses.The difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically significant(P<0.001).CONCLUSION This study showed that cell transplantation has a safe,effective and promising future in the management of TBI.

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

The Effect of Online Wellness Coaching for Nursing Students during the COVID-19 Lockdown on Well-Being: A Qualitative Study

Aim:The aim of this study was to explore and describe the lived experience of 3rd-year nursing students who participated in an online wellness coaching program during the COVID-19 pandemic lockdown.Methods:This qualitative research study on an online wellness coaching program included 30 female students,aged 21 to 30 years,who were confined to their home during the COVID-19 outbreak for two months.The students were asked to describe their feelings and responses during the COVID-19 lockdown.Results:Four thematic clusters emerged in the data analysis:what the students felt during the quarantine period,what the wellness coaching practice added to the students’lives,what changes resulted from the application and whether the students would like the application to continue and recommend the application.The study showed that students had a high level of stress,fear and anxiety at home during the COVID-19 outbreak.With the online wellness coaching application,they experienced a decrease in social isolation,an improved ability to cope with stress,and improved positivity and well-being.Conclusion:Findings from this study demonstrate that online wellness coaching during the COVID-19 quarantine has a positive effect on students’well-being.

Biological activities of the Ornithogalum orthophyllum and its in silico ADMET profile

Background:The bulbs and aerial parts of Ornithogalum are used in Turkey both as food and to treat various ailments,and some of its medical applications are well known.However,the biological activities of Ornithogalum orthophyllum have not yet been investigated.The objective of this study was to examine the antioxidant,urease and cholinesterase enzyme inhibition,and cytotoxic activities of different extracts obtained from the bulb and aerial parts of the O.orthophyllum plant.In addition,the absorption,distribution,metabolism,excretion,and toxicity properties of some phenolic compounds in plants were examined in silico.Methods:The antioxidant activity of the extracts obtained from the aerial parts of O.orthophyllum was investigated using the 2,2-diphenyl-1-picrylhydrazyl,2,2-azinobis(3-ethylbenzothiazoline-6-sulphonic acid),ferric reducing antioxidant power,and cupric reducing antioxidant capacity methods.Urease and cholinesterase enzyme inhibition were determined by using the indophenol and Ellman methods,respectively.The cytotoxic activity of the extracts was measured using a test based on the luminometric readings of the adenosine triphosphate levels of the cells.pkCSM,a free online web server(http://structure.bioc.cam.ac.uk/pkcsm)was used to predict the properties of the compounds analyzed.Results:The methanol extract of the aerial parts of O.orthophyllum was observed to have strong antioxidant and acetylcholinesterase enzyme inhibition potential.The petroleum ether extract of the aerial parts showed the highest anti-urease activity.The chloroform extract of the aerial parts exhibited the highest cytotoxic effect against A431 human epidermoid carcinoma cells.The absorption percentages of protocatechuic acid,p-hydroxybenzoic acid,vanillic acid,and p-coumaric acid compounds from the small intestine were between 71.17%and 93.49%,which were quite high.All the compounds were predicted to be unable to penetrate the central nervous system due to their inability to cross the blood-brain barrier.Not all compounds analyzed were predicted to have mutagenic,hepatotoxic,or minnow toxicity effects.Conclusion:The extracts obtained from the aerial parts of O.orthophyllum have strong biological activity and contain compounds that are well-absorbed and do not have mutagenic,hepatotoxic,or minnow toxicity effects,suggesting that they can be used as natural medicinal and nutritional sources in the future.

Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours

Neuroendocrine tumors(NETs)are a rare and heterogeneous disease group and constitute 0.5%of all malignancies.The annual incidence of NETs is increasing worldwide.The reason for the increase in the incidence of NETs is the detection of benign lesions,incidental detection due to the highest use of endoscopic and imaging procedures,and higher recognition rates of pathologists.There have been exciting developments regarding NET biology in recent years.Among these,first of all,somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis,hormone secretion,and proliferation.Subsequently,activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism.Finally,the importance of proangiogenic factors(platelet-derived growth factor,vascular endothelial growth factor,fibroblastic growth factor,angiopoietin,and semaphorins)in the progression of NET has been determined.Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Acarbose is again on the stage

Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments have been preferred over the last 10 to 15 years,the use of acarbose is not as common in treating type 2 diabetes as before.Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1(GLP-1).The positive effect of acarbose on GLP-1,and increasing evidence that it provides cardiovascular protection,suggests that acarbose may again be considered among the first-choice antidiabetic agents,as it was in the 1990s.

Comparison of body mass index, anti-müllerian hormone and insulin resistance parameters among different phenotypes of polycystic ovary syndrome

Background:Diagnosis of polycystic ovary syndrome(PCOS)depends on 2003 Rotterdam Criteria.According to these criteria there are four possible combinations resulting in various phenotypes.We aimed(i)to confirm that the levels of body mass index(BMI),anti-müllerian hormone(AMH)levels and insulin resistance(IR)are higher in PCOS patients and higher in phenotype-A among PCOS patients,and(ii)to determine cut-off values for the diagnosis of PCOS and phenotype-A.Materials and methods:This study was conducted in an IVF Center,between November 2019 and January 2021.Data of infertile women participating in the study was evaluated retrospectively.Parameters such as menstruation pattern,clinical hyperandrogenism,age,BMI,follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol,thyroid stimulating hormone(TSH),prolactin,AMH,dehydroepiandrosterone sulphate(DHEA-S),fasting blood glucose,fasting insulin levels,antral follicle counts(AFC)and ovarian volumes were recorded for each patient.Women were grouped as PCOS and non-PCOS,and PCOS group was further divided into 4 subgroups according to their phenotypes.Data of infertile patients with PCOS patients were compared with infertile non-PCOS patients and PCOS phenotypes were compared among each other.Results:Data of 244 infertile patients was included in the study.BMI,AMH,AFC,and HOMA-IR were statistically higher in PCOS patients,compared to non-PCOS patients.We found the AMH level of>3.105 ng/ml to be having 90.8%sensitivity and 90%specificity to diagnose a patient as PCOS.Among different phenotypes,also BMI,AMH,and insulin resistance index(HOMA-IR)levels were significantly higher in infertile PCOS phenotype-A when compared to other three phenotypes(p:0.003,p:0.000,and p:0.000,respectively).The AMH cut-off value to estimate phenotype-A was found as 6.095 ng/ml with 69.2%sensitivity and 86.7%specificity.We did not found threshold levels of BMI and HOMA-IR with high sensitivity to identify phenotype-A.Conclusion:Properly diagnosing PCOS and determining the phenotype are crucial due to the long-term health conditions.Therefore,we suggest that serum AMH level could be included in PCOS diagnosis criteria,and the value of 3.105 ng/ml would have a 90.8%sensitivity and 90%specificity.Also,to identify phenotype-A,AMH level could be used.Therefore,we speculate that AMH may serve to identify PCOS and PCOS phenotype-A in places where ultrasound imaging is not straightforward to perform or not easily accessible.

Pediatric dysphagia overview:best practice recommendation study by multidisciplinary experts

Background Currently,there is no comprehensive and multidisciplinary recommendation study covering all aspects of pediatric dysphagia(PD).This study aimed to generate PD management recommendations with methods that can be used in clinical practice to fill this gap in our country and in the world,from the perspective of experienced multidisciplinary experts.Methods This recommendation paper was generated by a multidisciplinary team,using the seven-step process and a three-round modified Delphi survey via e-mail.First,ten open-ended questions were created,and then detailed recommendations including management,diagnosis,treatment,and follow-up were created with the answers from these questions.Each recommendation item was voted on by the experts as overall consensus(strong recommendation),approaching consensus(weak recommendation)and divergent consensus(not recommended).Results In the 1st Delphi round,a questionnaire of 414 items was prepared based on the experts’responses to ten open-ended questions.In the 2nd Delphi round,59.2%of these items were accepted as pre-recommendation.In the 3rd Delphi round,62.6%of 246 items were accepted for inclusion in the proposals.The final version recommendations consisted of 154 items.Conclusions This study includes comprehensive and detailed answers for every problem that could be posed in clinical practice for the management of PD,and recommendations are for all pediatric patients with both oropharyngeal and esophageal dysphagia.