Exploring the Effect of Trataka (A Yogic Cleansing Technique) and Cold Eye Pack on Eye Strain During COVID-19 Pandemic: A Randomized Three-Arm Trial.

Objective: Computer vision syndrome is a major global public health concern affecting >60 million individuals globally. Yoga and naturopathy practices can reduce visual fatigue and strain. The present study attempted to explore the effect of trataka that is, a yogic cleansing technique and cold eye pack on visual strain and fatigue. Subjects: Three hundred volunteers from an IT company were recruited following inclusion and exclusion criteria. Intervention: The subjects were randomly distributed in three groups, that is, trataka, cold eye pack, and waitlist control group with an allocation ratio of 1:1:1. Outcome measure: Visual Fatigue Scale and Visual symptoms checklist (VSC) was administered at baseline and end of 2 weeks. Repeated measures analysis of variance (RM-ANOVA) with Bonferroni corrections was used to test the difference across the groups. Results: All the variables were similar at the baseline among the groups. Significant changes in the within-group analysis occurred in both the trataka and cold eye pack groups. The RM-ANOVA revealed significant differences in the VAS and VSC (p = 0.001) and the post hoc analysis suggested that there were significant differences in both the trataka and cold eye pack group when compared with the control group (p = 0.001); however, there was no differences between the trataka and cold eye pack group in both the scales (p = 1). Conclusions: The results of the present study suggest that a trataka and cold eye pack for 14 days improves self-rated visual strain and fatigue among IT professionals with computer vision syndrome. Clinical Trial registration number: CTRI/2020/11/029003.

Anatomical Description of Anterior Parametrium: A Probable Answer to Pelvic Recurrence Following Radical Hysterectomy.

A prospective analysis of a retrospective data of patients with cervix carcinoma treated by minimal invasive surgery at high-volume gynecology oncology center analyzing that minimal access surgery is an acceptable treatment modality in cervix carcinoma. The study included 423 patients who underwent laparoscopic/robotic radical hysterectomy after pre-operative evaluation after taking their consent and obtaining ethical approval from the IRB. Post-operatively, patients were followed up at regular intervals for clinical examination and ultrasonography for a median range of 36 months. A PET scan was done only if there was any suspicious finding on clinical examination or ultrasonography. Patients with parametrial involvement, positive vaginal margins, and nodal involvement were treated with chemotherapy/radiotherapy. Four hundred twenty-three patients of cervix carcinoma were treated with minimal access surgery. Average duration of surgeries was 92 min. Median range of duration of post-operative follow-up was 36 months. None of the patients had positive resection margins indicating adequate parametrectomy with complete oncological clearance. On post-operative follow-up, only 2 patients had vaginal recurrence which is comparable to that observed in open surgery and no pelvic recurrence. With the understanding of the anatomical landmarks of the anterior parametrium and development of skills for adequate oncological clearance, minimal access surgery should be the preferred surgical modality in carcinoma of the cervix.

A Novel Dynamic Bit Rate Analysis Technique for Adaptive Video Streaming over HTTP Support.

Recently, there has been an increase in research interest in the seamless streaming of video on top of Hypertext Transfer Protocol (HTTP) in cellular networks (3G/4G). The main challenges involved are the variation in available bit rates on the Internet caused by resource sharing and the dynamic nature of wireless communication channels. State-of-the-art techniques, such as Dynamic Adaptive Streaming over HTTP (DASH), support the streaming of stored video, but they suffer from the challenge of live video content due to fluctuating bit rate in the network. In this work, a novel dynamic bit rate analysis technique is proposed to model client-server architecture using attention-based long short-term memory (A-LSTM) networks for solving the problem of smooth video streaming over HTTP networks. The proposed client system analyzes the bit rate dynamically, and a status report is sent to the server to adjust the ongoing session parameter. The server assesses the dynamics of the bit rate on the fly and calculates the status for each video sequence. The bit rate and buffer length are given as sequential inputs to LSTM to produce feature vectors. These feature vectors are given different weights to produce updated feature vectors. These updated feature vectors are given to multi-layer feed forward neural networks to predict six output class labels (144p, 240p, 360p, 480p, 720p, and 1080p). Finally, the proposed A-LSTM work is evaluated in real-time using a code division multiple access evolution-data optimized network (CDMA20001xEVDO Rev-A) with the help of an Internet dongle. Furthermore, the performance is analyzed with the full reference quality metric of streaming video to validate our proposed work. Experimental results also show an average improvement of 37.53% in peak signal-to-noise ratio (PSNR) and 5.7% in structural similarity (SSIM) index over the commonly used buffer-filling technique during the live streaming of video.

Effect of mode of administration on Edinburgh Postnatal Depression Scale in the South Indian population: A comparative study on self-administered and interviewer-administered scores.

BACKGROUND: Edinburgh Postnatal Depression Scale (EPDS) is a validated screening tool widely used to assess perinatal depression (PND). However, due to stigma associated with PND, respondents could answer sensitive questions differently depending on the mode of administration, especially in culturally and linguistically diverse country like India. The present study explored longitudinal differences in EPDS scores between self-administered and interviewer-administered modes. METHODS: 177 women from rural South India were administered EPDS, self-administration followed by interviewer-administered for four visits, twice each during prenatal and postnatal visits. EPDS scores were compared between the two modes descriptively, graphically and by repeated mixed measure models. Classification of antenatal depression (AD), postnatal depression (PD) and PND based on the two modes were compared by McNemar Chi-square test. Clinical and psychosocial characteristics were examined to identify factors associated with differences in the scoring modes. Concordance rates and Goodman Kruskal's Gamma coefficients were measured for individual EPDS items. RESULTS: Longitudinal EPDS scores and rates of AD, PD and PND were significantly higher in self-administered mode. Recent adverse life events were the only factor observed to be significantly associated with the differences between the two modes. Rank correlation and concordance rates suggested stronger association for EPDS items relating to anhedonia subscale and moderate/weaker association for EPDS items relating to anxiety/depression subscales. CONCLUSION: Our study findings suggest that the effect of mode of administration should be taken into account while using PND screening tools such as EPDS, especially in countries such as India with higher levels of illiteracy.

Identification of clinical and psychosocial characteristics associated with perinatal depression in the south Indian population.

BACKGROUND: Longitudinal perinatal depression (PND) data is sparsely available in the Indian population. We have employed Edinburgh Postnatal Depression Scale (EPDS) to assess the prevalence and identify characteristics associated with PND in the south Indian population. PND was assessed longitudinally using EPDS scores with traditional cut-off approach as well as a novel method of latent class mixture modeling (LCMM). The LCMM method, to the best of our knowledge, has been used for the first time in the Indian population. METHODS: Three hundred and forty seven women, predominantly from economically-weaker sections of rural and urban South India were longitudinally assessed for antenatal depression (AD) and postnatal depression (PD) using EPDS cutoff-scores ≥13 and ≥10, respectively. Uni/multivariable analyses were used to identify PND associated characteristics. LCMM was then implemented, followed by risk characteristics identification. RESULTS: PND prevalence from traditional approach was 24.50 % (12.68 % AD; 18.16% PD). Characteristics associated with PND were urban-site and recent adverse life events. Irregular menstrual history and chronic health issues were associated with AD and PD, respectively. Three distinct PND trajectories were observed from LCMM-analysis: low-risk (76.08%), medium-risk (19.89%) and high-risk (4.04%). Urban-site, recent adverse life events, irregular menstrual history and pregnancy complications were associated with medium-risk/high-risk trajectories. LIMITATIONS: EPDS is a screening tool and not a diagnostic tool for depression. Since the study population included women from economically-weaker sections, the results need verification in other socio-economic groups. CONCLUSIONS: Both the traditional cut-off-based approach and LCMM provided very similar conclusions regarding the prevalence of PND and characteristics associated with it. Higher PND prevalence was observed in urban women compared to rural women. In low-income countries, identifying risk characteristics associated with PND is a critical component in designing prevention strategies for PND related conditions because of the limited access to mental health resources.

External Cephalic Version: A Dying Art Worth Reviving.

PURPOSE: Breech presentation is the most common abnormal presentation occurring in 3-4% of all deliveries. Incidence of caesarean section for breech presentation has increased markedly in the last few decades. Attempting external cephalic version (ECV) reduces the chance of non-cephalic presentation at term, thus reducing the rate of caesarean sections. METHODS: Prospective study was conducted in secondary healthcare centre, in rural set-up from August 2013 to August 2015. A total of 52 patients were enrolled into the study. RESULTS: ECV was successful in 32 out of 52 patients with overall success of 61.5%. Out of the 32 successful ECVs, 24 patients delivered vaginally (75%) (p value 0.00), 6 patients delivered by caesarean section, and 2 patients were lost to follow-up. Transverse lie had 100% success rate for ECV (p value 0.005). Gravidity, placental position, gestational age and use of tocolytics did not influence the success rate of ECV. Most common problem observed during the procedure was abdominal discomfort. CONCLUSION: ECV is a safe procedure with high percentage of patients delivering vaginally after successful version. Hence, acquiring skills in ECV should be considered mandatory in the postgraduate training of future obstetricians.

Retraction Note: Selective killing of cancer cells by a small molecule targeting the stress response to ROS.

This Letter is being retracted owing to issues with Fig. 1d and Supplementary Fig. 31b, and the unavailability of original data for these figures that raise concerns regarding the integrity of the figures. Nature published two previous corrections related to this Letter1,2. These issues in aggregate undermine the confidence in the integrity of this study. Authors Michael Foley, Monica Schenone, Nicola J. Tolliday, Todd R. Golub, Steven A. Carr, Alykhan F. Shamji, Andrew M. Stern and Stuart L. Schreiber agree with the Retraction. Authors Lakshmi Raj, Takao Ide, Aditi U. Gurkar, Anna Mandinova and Sam W. Lee disagree with the Retraction. Author Xiaoyu Li did not respond.

Immediate Versus Delayed Loading of Implant for Replacement of Missing Mandibular First Molar: A Randomized Prospective Six Years Clinical Study.

INTRODUCTION: Emergence of dental implants made the replacement of missing tooth easy. During the early days of introduction, implants were loaded three to six months after implant insertion, but understanding of healing cascade and improved production technology has changed the phase of restoration from delayed to immediate loading. AIM: To evaluate and compare the clinical outcome of immediate and delayed loaded implant supported prosthesis for missing mandibular first molar. The objectives were bleeding on probing, probing depth, implant mobility, marginal bone level and peri-implant radiolucency were evaluated during follow up period. MATERIALS AND METHODS: Twenty patients were included in this study who were in the need of fixed implant supported prosthesis for missing mandibular first molar. Single tooth implant with immediate loading done within two days of implant insertion in one group and another group were loaded after three months of implant insertion. These groups were evaluated clinically and radiographically over a period of 72 months after loading using Wilcoxon matched pairs test and Mann-Whitney U test. RESULTS: The study consists of 14 male and six female patients with the age range of 19 to 31 years. There was no bleeding on probing and probing depth remained well within the normal range even after 72 months of loading among both the groups. Minimal marginal bone loss observed with no mobility and peri-implant radiolucency. CONCLUSION: Implant supported prosthesis for missing mandibular first molar with immediate loading can be used as a successful treatment modality. It reduces treatment time, provides early function and prevents undue migration of adjacent tooth. Immediate loading showed similar clinical and radiographic results as that of delayed loading, indicating it as an equally efficient technique for implant supported prosthesis.

Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing.

Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for the treatment of neurological disorders, such as Huntington's disease. Small, endogenous vesicles known as exosomes have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load into exosomes upon co-incubation, without altering vesicle size distribution or integrity. Exosomes loaded with hsiRNAs targeting Huntingtin mRNA were efficiently internalized by mouse primary cortical neurons and promoted dose-dependent silencing of Huntingtin mRNA and protein. Unilateral infusion of hsiRNA-loaded exosomes, but not hsiRNAs alone, into mouse striatum resulted in bilateral oligonucleotide distribution and statistically significant bilateral silencing of up to 35% of Huntingtin mRNA. The broad distribution and efficacy of hsiRNA-loaded exosomes delivered to brain is expected to advance the development of therapies for the treatment of Huntington's disease and other neurodegenerative disorders.

YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression.

Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte quiescence and differentiation. Importantly, treatment with small interfering RNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of the positional identity of hepatocytes, supports targeting of YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype that is potentially responsive to this approach.

Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress.

The Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of cellular activities, including those involved in tumour metastasis and apoptosis. Here we identify an indispensable function of ROCK1 in metabolic stress-induced autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal component of the phosphoinositide 3-kinase class III lipid-kinase complex that induces autophagy, as an interacting partner of ROCK1. Upon nutrient deprivation, activated ROCK1 promotes autophagy by binding and phosphorylating Beclin1 at Thr119. This results in the specific dissociation of the Beclin1-Bcl-2 complex without affecting the Beclin1-UVRAG interaction. Conversely, inhibition of ROCK1 activity increases Beclin1-Bcl-2 association, thus reducing nutritional stress-mediated autophagy. Genetic knockout of ROCK1 function in mice also leads to impaired autophagy as evidenced by reduced autophagosome formation. These results show that ROCK1 acts as a prominent upstream regulator of Beclin1-mediated autophagy and maintains a homeostatic balance between apoptosis and autophagy.

A network of transcription factors operates during early tooth morphogenesis.

Improving the knowledge of disease-causing genes is a unique challenge in human health. Although it is known that genes causing similar diseases tend to lie close to one another in a network of protein-protein or functional interactions, the identification of these protein-protein networks is difficult to unravel. Here, we show that Msx1, Snail, Lhx6, Lhx8, Sp3, and Lef1 interact in vitro and in vivo, revealing the existence of a novel context-specific protein network. These proteins are all expressed in the neural crest-derived dental mesenchyme and cause tooth agenesis disorder when mutated in mouse and/or human. We also identified an in vivo direct target for Msx1 function, the cyclin D-dependent kinase (CDK) inhibitor p19(ink4d), whose transcription is differentially modulated by the protein network. Considering the important role of p19(ink4d) as a cell cycle regulator, these results provide evidence for the first time of the unique plasticity of the Msx1-dependent network of proteins in conferring differential transcriptional output and in controlling the cell cycle through the regulation of a cyclin D-dependent kinase inhibitor. Collectively, these data reveal a novel protein network operating in the neural crest-derived dental mesenchyme that is relevant for many other areas of developmental and evolutionary biology.

Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development.

Bmp4 expression is tightly regulated during embryonic tooth development, with early expression in the dental epithelial placode leading to later expression in the dental mesenchyme. Msx1 is among several transcription factors that are induced by epithelial Bmp4 and that, in turn, are necessary for the induction and maintenance of dental mesenchymal Bmp4 expression. Thus, Msx1(-/-) teeth arrest at early bud stage and show loss of Bmp4 expression in the mesenchyme. Ectopic expression of Bmp4 rescues this bud stage arrest. We have identified Tbx2 expression in the dental mesenchyme at bud stage and show that this can be induced by epithelial Bmp4. We also show that endogenous Tbx2 and Msx1 can physically interact in mouse C3H10T1/2 cells. In order to ascertain a functional relationship between Msx1 and Tbx2 in tooth development, we crossed Tbx2 and Msx1 mutant mice. Our data show that the bud stage tooth arrest in Msx1(-/-) mice is partially rescued in Msx1(-/-);Tbx2(+/-) compound mutants. This rescue is accompanied by formation of the enamel knot (EK) and by restoration of mesenchymal Bmp4 expression. Finally, knockdown of Tbx2 in C3H10T1/2 cells results in an increase in Bmp4 expression. Together, these data identify a novel role for Tbx2 in tooth development and suggest that, following their induction by epithelial Bmp4, Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity that leads to EK formation and to mesenchymal Bmp4 expression at the key bud-to-cap stage transition.

Selective killing of cancer cells by a small molecule targeting the stress response to ROS.

Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.

Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage.

Although apoptosis triggered by ultraviolet B (UVB)-mediated activation of the c-Jun N-terminal kinase (JNK) pathway is mediated by both intrinsic and extrinsic pathways, the mechanism of initiation of JNK activation remains obscure. Here, we report the characterization of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification. Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway. Moreover, phosphorylation of JIP-3 by ROCK1 was crucial for the recruitment of JNK. Inhibition of the activity of ROCK1 in keratinocytes resulted in decreased activation of the JNK pathway and thus a reduction in apoptosis. ROCK1(+/-) mice exhibited decreased UVB-mediated activation of JNK and apoptosis relative to wild-type mice. Our findings present a new molecular mechanism by which ROCK1 functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer.

Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation.

A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger (Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes. Thus, p53 activation results in cell-cycle arrest in Hzf wild-type MEFs, while in Hzf(-/-) MEFs, apoptosis is induced. Exposure of Hzf null mice to ionizing radiation resulted in enhanced apoptosis in several organs, as compared to in wild-type mice. These findings provide novel insights into the regulation of p53 transactivation function and suggest that Hzf functions as a key player in regulating cell fate decisions in response to genotoxic stress.