The physical-mechanical behavior and chemical bonding nature of poly-N-vinylpyrrolidone modified cement concrete.

In this study, the various amounts of poly-N-vinylpyrrolidone (PVPr) were added to the cement paste, and some parameters - flowing, initial and final setting points, water absorption, compressive strength, and flexural strength were determined. The concrete containing 0.8% PVPr exhibited high water absorption, specifically, at 14 and 28 days, increased from 15.65% to 20.71% and from 16.74% to 21.67%, respectively. The final setting time increased from 238 min to 261 min. It was determined that the compressive strength of the cement mortar increased from 54.8 MPa to 58.5 MPa when the PVPr content was 0.8-1.0%. The flexural strength also improved due to the presence of PVPr, increasing from 11.58 MPa to 14.27 MPa. According to the FTIR characterization, the PVPr macromolecule interacts with Ca2+ and Al3+ ions. TGA analysis reveals that the chemical interaction of PVPr with calcium and aluminum ions limits its mass loss up to 4-5% until 400 °C.

Spectral insights: Navigating the frontiers of biomedical and microbiological exploration with Raman spectroscopy.

Raman spectroscopy (RS), a powerful analytical technique, has gained increasing recognition and utility in the fields of biomedical and biological research. Raman spectroscopic analyses find extensive application in the field of medicine and are employed for intricate research endeavors and diagnostic purposes. Consequently, it enjoys broad utilization within the realm of biological research, facilitating the identification of cellular classifications, metabolite profiling within the cellular milieu, and the assessment of pigment constituents within microalgae. This article also explores the multifaceted role of RS in these domains, highlighting its distinct advantages, acknowledging its limitations, and proposing strategies for enhancement.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep

Abstract Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Resumo Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model

Abstract Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Resumo A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep / Mutações no gene da proteína morfogenética óssea 15 causadoras de defeitos na secreção proteica em ovelhas inférteis Cholistani

Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model / Potencial terapêutico de células-tronco e melatonina na redução da fibrose hepática induzida por CCl4 no modelo de ratos experimentais

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. METHODS AND RESULTS: The National Cardiogenic Shock Initiative (NCT03677180) is a single-arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI-CS. The primary end point was in-hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out-of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. CONCLUSIONS: Early use of MCS in AMI-CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

Nail breakage in patients with hypertrophic pseudoarthrosis after subtrochanteric femur fracture: treatment with exchanging nail and decortication.

In this study, we aimed to show the results of exchange nail and decortication in patients whose subtrochanteric femur fractures were treated with intramedullary nails and subsequently developed fracture nonunion and nail breakage com- plications. This study consisted of patients presenting with subtrochanteric femur fractures between January 2013 and April 2019 who underwent surgery and later experienced nail breakage due to hypertrophic nonunion. There were a total of 10 patients aged 26-62 years (Avg 40,30, SD: 9,989). Nine patients were smokers, and 1 patient had diabetes and hypertension. Three patients were admitted to the trauma center due to a car accident and 7 patients were admitted because of a fall. The infection parameters of all patients were normal. All patients had pathological movement complications and pain at the fracture site. Preoperatively, medulla diameter was measured with standard radiography in all patients. The diameters of the old nails applied to the patients ranged from 10 to 12 mm, and the diameters of the newly applied nails ranged from 14 to 16 mm. The fracture lines of all patients were opened to remove the broken nails, and decortication was performed. No additional autograft or allograft was applied to any patient. Union was achieved in all patients. We conclude that the use of larger diameter nails in conjunction with decortication will prevent nail breakage, improve healing and provide early union in patients with subtrochanteric femur fractures with hypertrophic pseudoarthrosis.

Cerebral blood flow and cerebrovascular resistance across the adult lifespan: A multimodality approach.

Cerebral blood flow (CBF) decreases across the adult lifespan; however, more studies are needed to understand the underlying mechanisms. This study measured CBF and cerebrovascular resistance (CVR) using a multimodality approach in 185 healthy adults (21-80 years). Color-coded duplex ultrasonography and phase-contrast MRI were used to measure CBF, CBF velocity, and vessel diameters of the internal carotid (ICA) and vertebral arteries (VA). MRI arterial spin labeling was used to measure brain perfusion. Transcranial Doppler was used to measure CBF velocity at the middle cerebral artery. Structural MRI was used to measure brain volume. CBF was presented as total blood flow (mL/min) and normalized CBF (nCBF, mL/100g/min). Mean arterial pressure was measured to calculate CVR. Age was associated with decreased CBF by ∼3.5 mL/min/year and nCBF by ∼0.19 mL/100g/min/year across the methods. CVR increased by ∼0.011 mmHg/mL/100g/min/year. Blood flow velocities in ICA and VA decreased with age ranging from 0.07-0.15 cm/s/year, while the vessel diameters remained similar among age groups. These findings suggest that age-related decreases in CBF can be attributed mainly to decreases in blood flow velocity in the large cerebral arteries and that increased CVR likely reflects the presence of cerebral vasoconstrictions in the small cerebral arterioles and/or capillaries.

Disparities in Decompressive Cranial Surgery Utilization in Severe Traumatic Brain Injury Patients without a Primary Extra-Axial Hematoma: A U.S. Nationwide Study.

OBJECTIVE: Decompressive craniectomy is recommended to reduce mortality in severe traumatic brain injury (TBI). Disparities exist in TBI treatment outcomes; however, data on disparities pertaining to decompressive craniectomy utilization is lacking. We investigated these disparities, focusing on race, insurance, sex, and age. METHODS: Hospitalizations (2004-2014) were retrospectively extracted from the Nationwide Inpatient Sample. The criteria included are as follows: age ≥18 years and indicators of severe TBI diagnosis. Poor outcomes were defined as discharge to institutional care and death. Multivariable logistic regression models were used to assess the effects of race, insurance, age, and sex, on craniectomy utilization and outcomes. RESULTS: Of 349,164 hospitalized patients, 6.8% (n = 23,743) underwent craniectomy. White (odds ratio [OR] = 0.50, 95% confidence interval [CI] = 0.44-0.57; P < 0.001) and Black (OR = 0.45, 95% CI = 0.32-0.64; P = 0.003) Medicare beneficiaries were less likely to undergo craniectomy. Medicare (P < 0.0001) and Medicaid beneficiaries (P < 0.0001) of all race categories had poorer outcomes than privately insured White patients. Black (OR = 1.2, 95% CI = 1.08-2.34; P = 0.001) patients with private insurance and Black (OR = 1.39, 95% CI = 1.22-1.58; P < 0.0001) Medicaid beneficiaries had poorer outcomes than privately insured White patients (P < 0.0001). Older patients (OR = 0.74, 95%, CI = 0.71-0.76; P < 0.001) were less likely to undergo craniectomy and were more likely to have poorer outcomes. Females (OR = 0.82, 95% CI = 0.76-0.88; P < 0.001) were less likely to undergo craniectomy. CONCLUSIONS: There are disparities in race, insurance status, sex, and age in craniectomy utilization and outcome. This data highlights the necessity to appropriately address these disparities, especially race and sex, and actively incorporate these factors in clinical trial design and enrollment.

Transcranial Doppler and computed tomography angiography for detecting cerebral vasospasm post-aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is a life-threatening complication following aneurysmal subarachnoid hemorrhage (aSAH). While digital subtraction angiography (DSA) is the current gold standard for detection, the diagnostic performance of computed tomography angiography (CTA) and transcranial Doppler (TCD) remains controversial. We aimed to summarize the available evidence and provide recommendations for their use based on GRADE criteria. A literature search was conducted for studies comparing CTA or TCD to DSA for adults ≥ 18 years with aSAH for radiographic vasospasm detection. The DerSimonian-Laird random-effects model was used to pool sensitivity and specificity and their 95% confidence intervals (CI) and derive positive and negative pooled likelihood ratios (LR + /LR -). Out of 2070 studies, seven studies (1646 arterial segments) met inclusion criteria and were meta-analyzed. Compared to the gold standard (DSA), CTA had a pooled sensitivity of 82% (95%CI, 68-91%) and a specificity of 97% (95%CI, 93-98%), while TCD had lower sensitivity 38% (95%CI, 19-62%) and specificity of 91% (95%CI, 87-94%). Only the LR + for CTA (27.3) reached clinical significance to rule in diagnosis. LR - for CTA (0.19) and TCD (0.68) approached clinical significance (< 0.1) to rule out diagnosis. CTA showed higher LR + and lower LR - than TCD for diagnosing radiographic vasospasm, thereby achieving a strong recommendation for its use in ruling in or out vasospasm, based on the high quality of evidence. TCDs had very low LR + and a reasonably low LR - , thereby achieving a weak recommendation against its use in ruling in vasospasm and weak recommendation for its use in ruling out vasospasm.

Aerobic exercise training and neurocognitive function in cognitively normal older adults: A one-year randomized controlled trial.

BACKGROUND: Current evidence is inconsistent on the benefits of aerobic exercise training for preventing or attenuating age-related cognitive decline in older adults. OBJECTIVE: To investigate the effects of a 1-year progressive, moderate-to-high intensity aerobic exercise intervention on cognitive function, brain volume, and cortical thickness in sedentary but otherwise healthy older adults. METHODS: We randomized 73 older adults to a 1-year aerobic exercise or stretching-and-toning (active control) program. The primary outcome was a cognitive composite score calculated from eight neuropsychological tests encompassing inductive reasoning, long-term and working memory, executive function, and processing speed. Secondary outcomes were brain volume and cortical thickness assessed by MRI, and cardiorespiratory fitness measured by peak oxygen uptake (VO2 ). RESULTS: One-year aerobic exercise increased peak VO2 by ∼10% (p < 0.001) while it did not change with stretching (p = 0.241). Cognitive composite scores increased in both the aerobic and stretching groups (p < 0.001 for time effect), although no group difference was observed. Total brain volume (p < 0.001) and mean cortical thickness (p = 0.001) decreased in both groups over time, while the reduction in hippocampal volume was smaller in the stretching group compared with the aerobic group (p = 0.040 for interaction). Across all participants, improvement in peak VO2 was positively correlated with increases in cognitive composite score (r = 0.282, p = 0.042) and regional cortical thickness at the inferior parietal lobe (p = 0.016). CONCLUSIONS: One-year aerobic exercise and stretching interventions improved cognitive performance but did not prevent age-related brain volume loss in sedentary healthy older adults. Cardiorespiratory fitness gain was positively correlated with cognitive performance and regional cortical thickness.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model.

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Spinal level and cord involvement in the prediction of sepsis development after vertebral fracture repair for traumatic spinal injury.

OBJECTIVE: Despite understanding the associated adverse outcomes, identifying hospitalized patients at risk for sepsis is challenging. The authors aimed to characterize the epidemiology and clinical risk of sepsis in patients who underwent vertebral fracture repair for traumatic spinal injury (TSI). METHODS: The authors conducted a retrospective cohort analysis of adults undergoing vertebral fracture repair during initial hospitalization after TSI who were registered in the National Trauma Data Bank from 2011 to 2014. RESULTS: Of the 29,050 eligible patients undergoing vertebral fracture repair, 317 developed sepsis during initial hospitalization. Of these patients, most presented after a motor vehicle accident (63%) or fall (28%). Patients in whom sepsis developed had greater odds of being male (adjusted OR [aOR] 1.5, 95% CI 1.1-1.9), having diabetes mellitus (aOR 1.5, 95% CI 1.11-2.1), and being obese (aOR 1.9, 95% CI 1.4-2.5). Additionally, they had greater odds of presenting with moderate (aOR 2.7, 95% CI 1.8-4.2) or severe (aOR 3.9, 95% CI 2.9-5.2) Glasgow Coma Scale scores and of having concomitant abdominal injuries (aOR 1.9, 95% CI 1.5-2.5) but not cranial, thoracic, or lower-extremity injuries. Interestingly, cervical spine injury was significantly associated with developing sepsis (OR 1.4, 95% CI 1.1-1.8), but thoracic and lumbar spine injuries were not. Spinal cord injury (OR 1.9, 95% CI 1.5-2.5) was also associated with sepsis regardless of level. Patients with sepsis were hospitalized approximately 16 days longer. They had greater odds of being discharged to rehabilitative care or home with rehabilitative care (OR 2.4, 95% CI 1.8-3.2) and greater odds of death or discharge to hospice (OR 6.0, 95% CI 4.4-8.1). CONCLUSIONS: Among patients undergoing vertebral fracture repair, those with cervical spine fractures, spinal cord injuries, preexisting comorbidities, and severe concomitant injuries are at highest risk for developing postoperative sepsis and experiencing adverse hospital disposition.

Venous Thromboembolism Risk and Outcomes Following Decompressive Craniectomy in Severe Traumatic Brain Injury: An Analysis of the Nationwide Inpatient Sample Database.

OBJECTIVE: Traumatic brain injury (TBI) is a risk factor for venous thromboembolism (VTE). The risk of VTE after decompressive craniectomy (DC) and its effects on the outcomes are unknown. We assessed the incidence of VTE, associated risk factors, and effects on the outcomes. METHODS: Using the National Inpatient Sample database, the hospitalizations of patients aged ≥18 years with a severe TBI diagnosis from 2004 to 2014 were extracted. The outcome was discharge status without mortality. Multivariable logistic and linear regressions were used. RESULTS: Of the 349,165 TBI hospitalizations, 23,813 (6.82%) had undergone DC and 14,175 (4.06%) had developed VTE. The VTE incidence was higher after DC compared with no DC (6.14% vs. 3.91%; P < 0.0001). DC (odds ratio [OR], 1.29; P < 0.005) was an independent predictor for the development of VTE. Age (OR, 1.26; P < 0.005), chronic lung disease (OR, 1.58; P < 0.05), electrolyte imbalance (OR, 1.43; P < 0.05), liver disease (OR, 0.10; P < 0.05), urinary tract infection (OR, 1.56; P < 0.05), pneumonia (OR, 2.03; P < 0.0001), and sepsis (OR, 1.57; P < 0.05) were significantly associated with the development of VTE. Obesity (OR, 2.09; P > 0.05) and spine injury (OR, 2.03; P > 0.05) showed a trend toward significance. VTE was associated with worse discharge outcomes (OR, 1.40; P < 0.05), longer lengths of stay (OR, 1.01; P < 0.00001), and higher costs (P < 0.0001). CONCLUSIONS: Our study showed an independent association between DC and an increased risk of VTE for patients with severe TBI. The development of VTE after DC increased the proportion of poor outcomes, prolonged the length of stay, and increased the hospitalization costs. Older patients with obesity, an electrolyte imbalance, chronic lung disease, spine injury, and infections were at a greater risk of VTE after DC. These risk factors could help in considering VTE prophylaxis for these patients.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep.

Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Predictors of thoracic and lumbar spine injuries in patients with TBI: A nationwide analysis.

OBJECTIVE: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI. METHODS: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression. RESULTS: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures. CONCLUSIONS: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI.

Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration.

There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington's disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

Extra-Axial Fluid Collections After Decompressive Craniectomy: Management, Outcomes, and Treatment Algorithm.

BACKGROUND: Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients. METHODS: We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature. RESULTS: Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P > 0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (ß = 0.56, P < 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management. CONCLUSIONS: Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

Thin Split Thickness Skin Grafting on Human Acellular Dermal Matrix Scaffold for the Treatment of Deep Burn Wounds.

BACKGROUND: Use of AlloDerm™ is highly suggested for the treatment of deep burns and burn sequela reconstruction. Scar formation and contracture are recognized as long-term consequences of split-thickness skin autografting, which is applied for full-thickness burn injuries. Mature fibroblasts, in the absence of dermis, seem to secrete collagen in the reformed scar pattern. OBJECTIVE: To process AlloDerm™ from fresh allograft and use it as a dermal substitute for covering deep wounds in burn patients and evaluate its effectiveness. METHODS: In this case-series, 7 patients with deep burn wounds involving different locations on the body surface were exposed to combined AlloDerm™ (processed from fresh human allograft) with thin split thickness skin autograft on it. On the 5th post-operative day, wound dressings were changed to evaluate the graft survival with the human acellular dermal matrix scaffold. To determine the skin profiles, follow-ups continued for at least 6 months. RESULTS: The results showed excellent graft take, good elasticity, acceptable thickness, and little contracture and scarring according to fix surgeon assessment in 6 patients. Graft rejection happened only in one patient with chronic electrical injury. CONCLUSION: AlloDerm™ derived from cadaver skin and combination of it with thin split thickness skin auto grafting constitute a cost-effective and favorable option for the treatment of deep burn wounds in our center, considering the increased tendency of the population towards organ donation in the event of brain death.