Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells

Two FDA-approved agents, ferumoxides (Feridex), a suspension of superparamagnetic iron oxide (SPIO) nanoparticles and protamine sulfate, a drug used to reverse heparin anticoagulation, can be complexed and used to label cells magnetically ex vivo. Labeling stem cells with ferumoxides-protamine sulfate (FePro) complexes allows for non-invasive monitoring by MRI. However, in order for stem cell trials or therapies to be effective, this labeling technique must not inhibit the ability of cells to differentiate. In this study, we examined the effect of FePro labeling on stem cell differentiation. Viability, phenotypic expression and differential capacity of FePro labeled CD34 + hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) were compared with unlabeled control cells. Colony-forming unit (CFU) assays showed that the capacity to differentiate was equivalent for labeled and unlabeled HSC. Furthermore, labeling did not alter expression of surface phenotypic markers (CD34, CD31, CXCR4, CD20, CD3 and CD14) on HSC, as measured by flow cytometry. SDF-1-induced HSC migration and HSC differentiation to dendritic cells were also unaffected by FePro labeling. Both FePro-labeled and unlabeled MSC were cultured in chondrogenesis-inducing conditions. Alcian blue staining for proteoglycans revealed similar chondrogenic differentiation for both FePro-labeled and unlabeled cells. Furthermore, collagen X proteins, indicators of cartilage formation, were detected at similar levels in both labeled and unlabeled cell pellets. Prussian blue staining confirmed that cells in labeled pellets contained iron oxide, whereas cells in unlabeled pellets did not. It is concluded that FePro labeling does not alter the function or differentiation capacity of HSC and MSC. These data increase confidence that MRI studies of FePro-labeled HSC or MSC will provide an accurate representation of in vivo trafficking of unlabeled cells.     

Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells

Photodynamic therapy (PDT) is a clinical approach that utilizes light-activated drugs for the treatment of a variety of pathologic conditions. Human poorly (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells undergo rapid apoptosis when treated with PDT sensitized with Hypocrellin A (HA) and Hypocrellin B (HB). It has been shown that these compounds have a strong photodynamic effect on tumors and viruses. The initiating events of PDT sensitized HA and HB-induced apoptosis are poorly defined. In the current study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HA and HB-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases-8 and -3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photoactivation of HA and HB enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/ CD95L expression appeared within 2 h following light activation and appeared to be a primary event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm is a secondary event following the activation of initiator caspase-8 preceding caspase-3 activation, cleavage of PARP and DNA fragmentation. Cytochrome c appeared in the cytosol within 2-3 h post PDT. Cleavage of PARP was observed at 3-4 h following PDT and caspase-3 specific inhibitor DEVD-CHO and broad-spectrum caspases inhibitor z-VAD-fmk blocked caspase-3 activation and PARP cleavage suggesting that caspase-3 plays an important role in HA and HB-induced apoptosis.     

A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases

Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.     

Impact of Mental Health Treatment on Suicide Attempts

This paper analyzes the impact of mental health treatment on suicide attempts. While prior work demonstrates the effectiveness of mental health treatment at reducing suicide risk, few studies examine nationally representative populations or use broad measures of access to mental health services. A methodological problem can arise in studies of mental health treatment and suicidal behavior because a suicide attempt can result in the use of more mental health services. Using nationally representative survey data combined with national estimates of provider availability, this paper employs a methodological correction to address that potential problem of reverse causation. This paper uses measures of the density of health care providers in an area as statistical instruments for use of mental health treatment in an analysis of the impact of mental health treatment on suicide attempts. This study finds that mental health treatment significantly reduces suicide attempts.

     

Medical Marijuana Laws,Marijuana Use,and Opioid-Related Outcomes among Women in the United States

BackgroundIn the context of the opioid epidemic, a limited but growing body of literature has found state medical marijuana laws (MMLs) to be associated with lower levels of opioid prescribing. However, robust evidence linking state MMLs with individual-level opioid-related outcomes is lacking, particularly among women. This finding is especially true for pregnant and parenting women, who have been disproportionately affected by the opioid crisis.MethodsUsing data drawn from the 2002–2014 National Survey on Drug Use and Heath, the study uses a difference-in-differences estimation strategy to compare opioid-related outcomes (opioid misuse initiation, opioid misuse in the past month and past year, and opioid use disorder) among all women, pregnant women, and parenting women in states with and without MMLs (before and after implementation). The study also investigates the impact of MMLs on marijuana use and marijuana use disorder.ResultsThe findings indicate that MMLs were not associated with opioid misuse, opioid misuse initiation, or opioid use disorder among all women, pregnant women, and parenting women. These laws were, however, positively correlated with marijuana use and marijuana use disorder among all women and women with children. In addition, MMLs were associated with an increase in the frequency of opioid misuse for pregnant women and a decrease in the frequency of opioid misuse for parenting women.ConclusionsThis finding suggests that, although medical marijuana may be viewed by some as a substitute for opioid analgesics, MMLs may not be an effective policy tool to tackle the opioid epidemic among women, especially pregnant and parenting women.     

Polyorchidism in ultrasound examination: A case report

Polyorchidism is usually diagnosed incidentally when the patient undergoes imaging or surgery for some other reason. Although we are facing lack of evidence in different steps of diagnostic and therapeutic workup of these patients, this disorder is usually considered benign, not requiring any intervention. We report the case of a man complaining of a palpable mass in his scrotum. We evaluated the patient using ultrasound, MRI and serum tumour marker level measurement. The patient was finally diagnosed with polyorchidism (three testes). For the management, we recommended annual physical examination, US examination and serum tumour marker level measurement.     

The effect of vitamin E on sperm motility and viability in asthenoteratozoospermic men: In vitro study

Induction of oxidative stress during the sperm preparation process for assisted reproductive techniques (ART) in men can weaken sperm parameters. Vitamin E (VE) is considered a factor in boosting male fertility. This experimental study (in vitro) aimed to assess the impact of VE supplementation on sperm quality and lipid peroxidation during sperm sampling at different times. For this mention, semen samples were collected from 50 asthenoteratozoospermic men. Samples were divided into control and test groups for 2, 4 and 6 hr that the test group was incubated with VE (2 mM). In two groups, total motility, progressive motility and viability based on the WHO 2010 criteria were assessed. Moreover, malondialdehyde (MDA) levels were evaluated in each group. In the control group, total and progressive motility and sperm viability were decreased significantly after 2 hr; however, MDA levels were increased significantly after 6 hr. Also, in the test group, sperm parameters were increased significantly after 2 hr, and MDA levels were decreased significantly after 6 hr compared to the control group. In outcome, in vitro VE supplementation may protect spermatozoa from the adverse effect of oxidative stress during sperm preparation via preservation antioxidant processes in normal condition.     

Review of COVID-19 and male genital tract

COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors’ expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.