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Background Trans-differentiation of human-induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons a likely significant advance for disease modeling and in vitro assay development. Recent single-cell interrogation of Ngn2-induced neurons, however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC-derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. Results Here, we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days), and the impact of hiPSC-N/hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAlNGN2&g=NES . Conclusions While overall we support the use of the investigated cellular models for the study of neuropsychiatric disease, we also identify important limitations. We hope that this work will contribute to understanding and optimizing cellular modeling for complex brain disorders.

Trans-differentiation of human induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons for disease modeling and in vitro assay development, a significant advance from previously used neoplastic and other cell lines. Recent single-cell interrogation of Ngn2-induced neurons however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. Here we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days) and of hiPSC-N / hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: nemoanalytics.org/p?l=DasEtAlNGN2&g=PRPH.

Compression ignition engines powered by diesel are the work horses of developing countries like India. However, burning fossil fuel causes a lot of air pollution and the depletion of fuel at an alarming rate. Fuels produced from biomass or wastes can partially substitute fossil diesel to decrease its consumption. One such feedstock is waste cooking oil (WCO) which can be easily converted into fuel for diesel engines. The hydrotreating process stands out among the methods available for converting WCO into fuel, since its properties are almost similar to fossil diesel with little or no oxygen content. In this study, the physico-chemical properties of the hydrotreated waste cooking oil (HVO), biodiesel of waste cooking oil, diesel and blends of HVO and diesel are compared. The blends were prepared by mixing 10%, 20%, 30%, 40% and 50% of HVO on volume basis in diesel. The evaporation rate and ignition probability of the fuel samples were found by using a hot-plate test setup. HVO had higher ignition probability than all the test sample. As the percentage of HVO increased in the test samples, the ignition probability increased. The Sauter mean diameter (SMD) of the samples was also found using Malvern Spraytec. The SMD of HVO was larger than diesel but smaller than biodiesel. The study shows that blends of HVO up to 30% are feasible for present use in diesel engines, as the viscosity (2.54, 2.59 and 2.62cSt) and calorific value (42.41, 42.29, 42.08 MJ/kg) of the three blends (10%, 20% and 30%) is close to diesel (2.51cSt and 42.58 MJ/kg). Also, due to high cetane index, neat HVO or blends having higher HVO content (> 30%) cannot be used in the existing engines as the engine power output may be affected. Therefore, to use these fuels, the engine needs to be modified which is not feasible for existing engines. The FTIR and GC-MS analysis shows that the HVO has low oxygen content and high amount of paraffins, whereas biodiesel of waste cooking oil has high unsaturation and high oxygen content.

The positive effect of decarbonizing the transport sector by using bio-based fuels is high. Currently, biodiesel and ethanol are the two biofuels that are blended with fossil fuels. Another technology, namely, hydroprocessing, is also gaining momentum for producing biofuels. Hydrotreated vegetable oil (HVO) produced using this process is a potential drop-in fuel due to its improved physiochemical properties. This study aimed to reduce the fossil diesel content by blending 20% and 30% HVO and 5%, 10% and 15% waste cooking oil biodiesel on a volume basis. The blends were used to conduct a thorough performance examination of a single-cylinder compression ignition engine. The thermal efficiency of the engine was enhanced by the addition of biodiesel to the blend. The efficiency increased as the proportion of biodiesel in the mix increased, although it was still less efficient than diesel. The maximum improvement in thermal efficiency of 4.35% was observed with 20% blending of HVO and 15% blending of biodiesel compared with 20% blending of HVO and diesel. However, the HC (decrease of 30%), CO (decrease of 23.5%) and smoke (decrease of 21.1%) emissions were observed to be the lowest with 30% blending of HVO and 15% blending of biodiesel. A fuzzy-logic-based Taguchi method and Grey’s method were then applied to find the best blend of HVO, biodiesel and diesel. The combination of the two methods made it easier to carry out multi-objective optimization. The brake thermal efficiency (BTE), smoke and NO emissions were selected as the output parameters to optimize the HVO and biodiesel blend. The optimization study showed that 30% blending of HVO and 15% blending of biodiesel was the best blend, which was authenticated using the confirmation experiment.

Pending a formal consensus on the clinical terminology encompassed under AFTF, terms such as recurrence, relapse, recalcitrance, and chronic persistence seem to represent its varied clinical presentations.[2] Authors used a term, “clinical resistance,” which in my opinion is different from AFTF (that should include facets of only clinical non- or suboptimal-response) and includes the dichotomy between the in vivo and in vitro response to a particular drug/therapy. The rationale of this distinction is the prevalent confusion amongst dermatologists, and the need for according weighted emphasis to contributing factors other than AFR, to harness the epidemic of AFTF in toto ·It is regrettable that ciclopirox (CPX), one of the most promising solutions to the emerging antifungal resistance, was not even mentioned; despite its approval for superficial mycoses having been given in 1985 and 1996 by the Drug Controller General of India and US-FDA, respectively. Not a single case of clinical or in vivo resistance to CPX has been reported despite more than three decades of its frequent use for tinea and mucocutaneous yeast infections globally.[3] Further, in vitro susceptibility to CPX of multiple strains of yeasts have been reported to be better than various azoles including itraconazole and ketoconazole.[4] The reported penetrance of topical CPX into the hair follicles and sebaceous glands [3] also offsets the problem of treatment failures potentially attributable to the recently elucidated dermatophytic invasion of vellus hair in tinea corporis.[5] Finally, laboratory and clinical studies reporting development of resistance and cross resistance of dermatophytes to ergosterol synthesis inhibitors (ESI) specifically itraconazole, terbinafine, and amorolfine following repeated subcultures in sub-inhibitory drug concentrations (in vitro) and prolonged clinical therapy with azoles (in vivo) respectively, failed to show emergence of resistance to CPX.[3] The two most important factors plausibly contributing to the above phenomenon include: 1) unique ESI-independent antifungal mechanism of CPX that involves inhibition of the trivalent metal ion-dependent enzymes leading to accumulation of intracellular peroxides, and 2) irreversible binding to intracellular structures rescuing CPX from drug efflux mechanisms.[3] The potent anti-inflammatory activity of CPX (equivalent to 2.5% hydrocortisone) is a boon, as cognizance of this fact can prevent prescription of steroid-based combination topicals that are often prescribed by clinicians to provide early relief to the patient; albeit at the cost of increasing the likelihood of therapeutic failure and the abuse of and dependence on such topicals by the patients.[3] ·The role of agricultural fungicides contributing to primary azole resistance was mentioned, but the Indian scenario was missed out.

Resilience refers to one's ability to overcome challenges. Mindfulness is an attitude of awareness and non-judgmentally accepting one's moment-to-moment experience. Flourishing includes a range of positive concepts and offers a more holistic construct to being well and happy. The purpose of this study was to explore the relationship between mindfulness, resilience and flourishing. The current study was conducted on 111 middle aged adults from the age of 40-60 years old. The results showed that mindfulness, resilience and flourishing were all significantly related to one another. It was also seen that those who were working were significantly more mindful and resilient than those who were not. Lastly, the results also showed that resilience and flourishing were predicted by mindfulness. The study has important implications for the field of positive psychology.

A 32-year-old man presented with uniform enlargement of right upper limb for 6 years. Examination revealed painful disorganised elbow joint along with sensory impairment in the affected limb with weakness of small muscles. The patient was given empirical antileprotic therapy from outside without any benefit. Ultrasonography showed pan-hypertrophic nature of local tissues. Although axonal type of sensorimotor neuropathy involving right ulnar and median nerve was detected in nerve conduction velocity study, biopsy of the same failed to confirm any axonal degeneration or evidence of leprosy. Considering the nature of sensory abnormality MRI of cervical spine was done which revealed a syrinx extending from C3 till D2. Tests for vasomotor tone showed positive results on the affected limb. Syringomyelia can rarely give rise to pan-hypertrophy of limb due to sympathetic overactivity, which is infrequently reported in literatures and deficient in logical grounds.

Glutathione is a low molecular weight thiol-tripeptide that plays a prominent role in maintaining intracellular redox balance. In addition to its remarkable antioxidant properties, the discovery of its antimelanogenic properties has led to its promotion as a skin-lightening agent. It is widely used for this indication in some ethnic populations. However, there is a dichotomy between evidence to support its efficacy and safety. The hype around its depigmentary properties may be a marketing gimmick of pharma-cosmeceutical companies. This review focuses on the various aspects of glutathione: its metabolism, mechanism of action and the scientific evidence to evaluate its efficacy as a systemic skin-lightening agent. Glutathione is present intracellularly in its reduced form and plays an important role in various physiological functions. Its skin-lightening effects result from direct as well as indirect inhibition of the tyrosinase enzyme and switching from eumelanin to phaeomelanin production. It is available in oral, parenteral and topical forms. Although the use of intravenous glutathione injections is popular, there is no evidence to prove its efficacy. In fact, the adverse effects caused by intravenous glutathione have led the Food and Drug Administration of Philippines to issue a public warning condemning its use for off-label indications such as skin lightening. Currently, there are three randomized controlled trials that support the skin-lightening effect and good safety profile of topical and oral glutathione. However, key questions such as the duration of treatment, longevity of skin-lightening effect and maintenance protocols remain unanswered. More randomized, double-blind, placebo-controlled trials with larger sample size, long-term follow-up and well-defined efficacy outcomes are warranted to establish the relevance of this molecule in disorders of hyperpigmentation and skin lightening.