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Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio-similar product Zybev(Z) for macular edema because of retinal diseases. Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio-similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks. Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre-injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 μm, and the post-injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 μm; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (μm) decreased from 11.85 ± 1.96 pre-injection to 10.52 ± 1.75 post-injection, and the mean average cube volume (mm3) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow-up period after injection, no patient had inflammation, endophthalmitis, an increase in intra-ocular pressure, or systemic side effects. Conclusion: This short-term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio-similar products of bevacizumab for the treatment of macular edema because of retinal diseases.

We are in the midst of the COVID-19 pandemic. Since December 2019, severe acute respiratory coronavirus (SARS-CoV-2) has infected more than half a billion people, killing nearly 7 million people worldwide. Now various variants of SARS-CoV-2 are causing mayhem and driving the global surge. Epidemiologists are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people and those with underlying health conditions who are considered high-risk are likely to suffer complications. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms of pharmacologic modification of the sympathetic and hypothalamic response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.

We report seven examples of a long-ignored type of confined solar flare eruption that does not fit the standard model for confined flare eruptions. Because they are confined eruptions, do not fit the standard model, and unexpectedly erupt in ostensibly inert magnetic arches, we have named them stealth non-standard-model confined flare eruptions. Each of our flaring magnetic arches stems from a big sunspot. We tracked each eruption in full-cadence UV and EUV images from the Atmospheric Imaging Assembly of Solar Dynamics Observatory (SDO) in combination with magnetograms from SDO’s Helioseismic and Magnetic Imager. We present the onset and evolution of two eruptions in detail: one of six that each makes two side-by-side main flare loops, and one that makes two crossed main flare loops. For these two cases, we present cartoons of the proposed pre-eruption field configuration and how sudden reconnection makes the flare ribbons and flare loops. Each of the seven eruptions is consistent with being made by sudden reconnection at an interface between two internal field strands of the magnetic arch, where they cross at a small (10°–20°) angle. These stealth non-standard-model confined flare eruptions therefore plausibly support the idea of E. N. Parker for coronal heating in solar coronal magnetic loops by nanoflare bursts of reconnection at interfaces of internal field strands that cross at angles of 10°–20°.

Solar coronal jets are frequently occurring collimated ejections of solar plasma, originating from magnetically mixed polarity locations on the Sun of size scale comparable to that of a supergranule. Many, if not most, coronal jets are produced by eruptions of small-scale filaments, or minifilaments, whose magnetic field reconnects both with itself and also with surrounding coronal field. There is evidence that minifilament eruptions are a scaled-down version of typical filament eruptions that produce solar flares and coronal mass ejections (CMEs). Moreover, the magnetic processes building up to and triggering minifilament eruptions, which is often flux cancelation, might similarly build up and trigger the larger filaments to erupt. Thus, detailed study of coronal jets will inform us of the physics leading to, triggering, and driving the larger eruptions. Additionally, such studies potentially can inform us of smaller-scale coronal-jet-like features, such as jetlets and perhaps some spicules, that might work the same way as coronal jets. We propose a high-resolution (∼0″. 1 pixels), high-cadence (∼5 s) EUV-solar-imaging mission for the upcoming decades, that would be dedicated to observations of features of the coronal-jet size scale, and smaller-scale solar features produced by similar physics. Such a mission could provide invaluable insight into the operation of larger features such as CMEs that produce significant Space Weather disturbances, and also smaller-scale features that could be important for coronal heating, solar wind acceleration, and heliospheric features such as the magnetic switchbacks that are frequently observed in the solar wind.

Purpose: To evaluate and compare endothelial cell changes in phacoemulsification and manual small-incision cataract surgery (MSICS) in patients with uncomplicated senile cataracts. Methods: This was a prospective, tertiary care hospital-based, randomized, double-blinded interventional study. In total, 152 patients with an uncomplicated senile cataract of nuclear grade III and above were recruited. Exclusion criteria included patients with preoperative endothelial cell density (ECD) less than 1500 cells/mm3, a history of previous ocular surgery, any other coexisting ocular disease, and intraoperative or postoperative surgical complications. Preoperative and postoperative values of ECD and central corneal thickness (CCT) were measured, analyzed, and correlated with various factors. Results: Patients were randomized into two interventional groups-MSICS and phacoemulsification. Factors associated with significant drop in postoperative ECD following phacoemulsification were patients with advanced age (P = 0.01), higher grades of cataract (P = 0.01), and longer effective phacoemulsification time (P = 0.007). Shallow anterior chamber depth (ACD) was strongly associated with greater ECD loss in both groups (P < 0.0001). A threshold value of 2.86 mm of ACD was defined for minimal endothelial cell loss following phacoemulsification. CCT was observed to slightly increase postoperatively in both groups but was insignificant (P > 0.05). Conclusion: Both MSICS and phacoemulsification have similar postoperative visual outcomes. An increase in postoperative CCT is insignificant following surgery. Greater postoperative ECD loss is associated with phacoemulsification with advanced age, hard nuclear cataracts, and longer effective phacoemulsification time. ACD can be used as an essential parameter preoperatively to determine the choice of surgical technique between MSICS and phacoemulsification.

We propose that coronal heating in EUV coronal plumes is weaker, not stronger, than in adjacent nonplume coronal magnetic funnels. This expectation stems from (i) the observation that an EUV plume is born as the magnetic flux at the foot of the plume’s magnetic funnel becomes tightly packed, and (ii) the observation that coronal heating in quiet regions increases in proportion to the coastline length of the underlying magnetic network. We do not rule out the possibility that coronal heating in EUV plumes might be stronger, not weaker, but we point out how the opposite is plausible. We reason that increasing coronal heating during plume birth would cause co-temporal increasing net upward mass flux in the plume, whereas decreasing coronal heating during plume birth would cause co-temporal net downward mass flux in quiet-region plumes and co-temporal decrease in net upward mass flux or even net downward mass flux in coronal-hole plumes. We further reason that conclusive evidence of weaker coronal heating in EUV plumes would strengthen the possibility that magnetic-twist waves from fine-scale magnetic explosions at the edges of the magnetic network (1) power much of the coronal heating in quiet regions, and (2) power most of the coronal heating and solar-wind acceleration in coronal holes, with many twist waves surviving to become magnetic field switchbacks in the solar wind from coronal holes.

Background and Aims: There is increasing awareness about an association between type 2 diabetes mellitus (T2DM) and male hypogonadism. However, data are sparse and less uniform with respect to factors associated with hypogonadism in males with T2DM. This study aimed to assess the frequency and correlates of hypogonadism in these subjects. Materials and Methods: This cross-sectional study included 130 males with T2DM, age 25-60 years. Study subjects were screened for hypogonadal symptoms using androgen deficiency in aging male (ADAM) questionnaire. Serum total testosterone was measured in subjects with positive ADAM score. Hypogonadism was defined as the presence of positive ADAM score and low serum total testosterone (

Sepsis due to multidrug resistant pathogens is the most common cause of death in intensive care units. Here, the authors report that fecal microbiota transplant (FMT) can rescue mice from lethal sepsis of pathogens isolated from stool of a critically ill patient and show that FMT reverses the immunosuppressive effect induced by the pathogen community.

We report high-resolution, high-cadence observations of five small-scale coronal jets in an on-disk quiet Sun region observed with Solar Orbiter’s EUI/HRI _EUV in 174 Å. We combine the HRI _EUV images with the EUV images of SDO/AIA and investigate the magnetic setting of the jets using coaligned line-of-sight magnetograms from SDO/HMI. The HRI _EUV jets are miniature versions of typical coronal jets as they show narrow collimated spires with a base brightening. Three out of five jets result from a detectable minifilament eruption following flux cancelation at the neutral line under the minifilament, analogous to coronal jets. To better understand the physics of jets, we also analyze five small-scale jets from a high-resolution Bifrost MHD simulation in synthetic Fe ix /Fe x emissions. The jets in the simulation reside above neutral lines and four out of five jets are triggered by magnetic flux cancelation. The temperature maps show evidence of cool gas in the same four jets. Our simulation also shows the signatures of opposite Doppler shifts (of the order of ±10 s of km s ^−1 ) in the jet spire, which is evidence of untwisting motion of the magnetic field in the jet spire. The average jet duration, spire length, base width, and speed in our observations (and in synthetic Fe ix /Fe x images) are 6.5 ± 4.0 min (9.0 ± 4.0 minutes), 6050 ± 2900 km (6500 ± 6500 km), 2200 ± 850 km, (3900 ± 2100 km), and 60 ± 8 km s ^−1 (42 ± 20 km s ^−1 ), respectively. Our observation and simulation results provide a unified picture of small-scale solar coronal jets driven by magnetic reconnection accompanying flux cancelation. This picture also aligns well with the most recent reports of the formation and eruption mechanisms of larger coronal jets.

The study of disease modules facilitates insight into complex diseases, but their identification relies on knowledge of molecular networks. Here, the authors show that disease modules and genes can also be discovered in deep autoencoder representations of large human gene expression datasets.

Purpose: To compare intracameral Ropivacaine to Lignocaine during phacoemulsification under augmented topical anesthesia, in terms of efficacy and safety. Methods: This prospective, randomized, double-masked clinical trial included subjects planned for phacoemulsification with posterior chamber intraocular lens implantation for visually significant uncomplicated senile cataract, under augmented topical anesthesia. Cases were randomized into two groups, Group A (Ropivacaine 0.1%) or Group B (Lignocaine 1.0%). The pain experienced by the patients during the surgery, mydriasis, post-op inflammation and endothelial cell change at six weeks after the procedure was evaluated. Surgeon's feedback was recorded to evaluate the cooperation of the patient during surgery. Results: A total of 210 subjects were screened and 184 were randomized to have 92 subjects in each group. There was no statistically significant difference seen on comparing Group A and B with respect to Age (P = 0.05), painful surgical steps (P = 0.85), visual analog scale scores (P = 0.65), surgeon's score (P = 0.11), postoperative inflammation (P = 0.90) and average ultrasound time during phacoemulsification (P = 0.10). Subjects in Group A fared better when compared to Group B with respect to endothelial cell loss (P = 0.0008), and augmentation in mydriasis (P < 0.001). Conclusion: Intracameral Ropivacaine and Lignocaine, both are equally effective in providing analgesia during phacoemulsification. However, intracameral Ropivacaine is superior to Lignocaine with regards to corneal endothelial cell safety, and augmenting mydriasis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a life-threating viral infection that is highly transmissible and be lethal. Although many patients with mild symptoms recover, an acute form of the infection is characterized by rapidly evolving respiratory failure, an acute inflammatory response, organ failure, and death. Herein, we describe the use of clonidine to modulate the acute inflammatory consequences of this infection in three cases. The patients were three men between 40–50 years from Kathmandu valley, during the peak of COVID-19 (September 2020- January 2021). All three patients presented with typical COVID-19 symptoms (daily fever, loss of smell and taste, excessive fatigue, cough) and had pneumonia with typical finding in CT Scan of chest. Patient 1was able to maintain adequate oxygenation despite having pneumonia, managed at home by regular self-monitoring of vitals and treatment with oral clonidine whereas patient 2 and 3 developed significant pneumonia and had difficult in maintaining oxygenation hence admitted in hospital and treated with clonidine and supplemental oxygen. All three patients recovered completely. In this limited report, we proposed several mechanisms by which clonidine may be useful in managing rapidly evolving SARS-CoV-2 infection based on the rationale that early clonidine administration can intervene in the catecholaminergic response that characterizes rapid clinical deterioration including presumptive cytokine storm that occurs in COVID-19 infection in vulnerable populations.

Aim: To generate local evidence to fill up the knowledge gap about the domestic violence faced by the antenatal females. Objectives: To screen for domestic violence in antenatal females. To explore association, if any, with socio-demographic and pregnancy related attributes among antenatal females of an urbanized village of Delhi. Materials and Methods: Socio demographic details and pregnancy related attributes and HITS (Hurt, Insult, Threaten, Scream) questionnaire for screening domestic violence was used on 165 pregnant females in a community based setting. Results: 23% of pregnant women were screened positive for domestic violence. Physical hurt was present among 60% of victims of domestic violence. The predictors for domestic violence among pregnant women as derived from logistic regression were – educational status of head of the family/husband, substance abuse by husband and history of previous abortions. Conclusion and Recommendations: More emphasis should be given on well being of the pregnant women who are victims of domestic violence. The policy makers and program managers should integrate social welfare schemes with the RCH program and all levels of health care functionaries should be sensitized about dealing with victims of domestic violence. Laws should be implemented effectively against perpetrators of domestic violence and more importantly females should be made aware of such laws and should be motivated to report it to the legal authorities and not to take up violence for granted.

A challenge in characterizing active region (AR) coronal heating is in separating transient (bursty) loop heating from the diffuse background (steady) heating. We present a method of quantifying coronal heating’s bursty and steady components in ARs, applying it to Fe xviii (hot 94) emission of an AR observed by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. The maximum-, minimum-, and average-brightness values for each pixel, over a 24 hr period, yield a maximum-brightness map, a minimum-brightness map, and an average-brightness map of the AR. Running sets of such three maps come from repeating this process for each time step of running windows of 20, 16, 12, 8, 5, 3, 1, and 0.5 hr. From each running window’s set of three maps, we obtain the AR’s three corresponding luminosity light curves. We find (1) the time-averaged ratio of minimum-brightness-map luminosity to average-brightness-map luminosity increases as the time window decreases, and the time-averaged ratio of maximum-brightness-map luminosity to average-brightness-map luminosity decreases as the window decreases; (2) for the 24 hr window, the minimum-brightness map’s luminosity is 5% of the average-brightness map’s luminosity, indicating that at most 5% of the AR’s hot 94 luminosity is from heating that is steady for 24 hr; (3) this upper limit on the fraction of the hot 94 luminosity from steady heating increases to 33% for the 30 minute running window. This requires that the heating of the 4–8 MK plasma in this AR is mostly in bursts lasting less than 30 minutes: at most a third of the heating is steady for 30 minutes.

Introduction: In schizophrenia, chemical pathophysiology is not fully understood. Hereditary, environmental free radicalinduced damage is the proposed mechanism associated with it. Drug-related complications in schizophrenia due to altered pro-oxidative and antioxidant homeostasis is the major concern for a psychiatrist. Aim: To evaluate changes in anthropometry and biochemical parameters by antipsychotic drugs and correlation between Serum Uric Acid (SUA) with other parameters before and after third and six months of treatment, in newly diagnosed schizophrenic patients. Materials and Methods: In this prospective, observational study based on ICD-10 criteria, 107 drug-naive schizophrenia patients were screened for weight, height, Body Mass Index (BMI), Waist Circumference (WC) as anthropometric variables, Blood Pressure (BP) and biochemical variables i.e., Fasting Blood Sugar (FBS), Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein Cholesterol (HDL-c) and uric acid at the time of diagnosis, then after 3rd and 6th months of treatment. Statistical analysis was performed using paired t-test and Pearson’s correlation coefficient. A p-value 4 mg/dL could be the ‘Red flag’ sign to trigger antioxidant SUA into pro-oxidant. These outcomes also provide a hypothetical basis for use of antioxidant supplementation as novel therapeutic strategies. Such implications could improve the prognosis and prevent future complication in schizophrenic patients.

ABSTRACT Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.

Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades intestinal collagen. Antibiotic administration is ineffective in addressing this issue as it inadvertently eliminates normal flora while allowing pathogenic bacteria to “bloom” and acquire antibiotic resistance. Compounds that could attenuate collagenase production while allowing commensal bacteria to proliferate normally would offer major advantages without the risk of the emergence of resistance. We have previously shown that intestinal phosphate depletion in the surgically stressed host is a major cue that triggers P. aeruginosa virulence which is suppressed under phosphate abundant conditions. Recent findings indicate that orally administered polyphosphate, hexametaphosphate, (PPi) suppresses collagenase, and biofilm production of P. aeruginosa and S. marcescens in animal models of intestinal injury but does not attenuate E. faecalis induced collagenolytic activity (Hyoju et al., 2017). Systemic administration of phosphates, however, is susceptible to rapid clearance. Given the diversity of collagenase producing bacteria and the variation of phosphate metabolism among microbial species, a combination therapy involving different phosphate compounds may be required to attenuate pathogenic phenotypes. To address these barriers, we present a drug delivery approach for sustained release of phosphates from poly(ethylene) glycol (PEG) hydrogel nanoparticles. The efficacy of monophosphate (Pi)- and PPi-loaded NPs (NP-Pi and NP-PPi, respectively) and a combination treatment (NP-Pi + NP-PPi) in mitigating collagenase and biofilm production of gram-positive and gram-negative pathogens expressing high collagenolytic activity was investigated. NP-PPi was found to significantly decrease collagenase and biofilm production of S. marcescens and P. aeruginosa. Treatment with either NP-Pi or NP-Pi + NP-PPi resulted in more prominent decreases in E. faecalis collagenase compared to NP-PPi alone. The combination treatment was also found to significantly reduce P. aeruginosa collagenase production. Finally, significant attenuation in biofilm dispersal was observed with NP-PPi or NP-Pi + NP-PPi treatment across all test pathogens. These findings suggest that sustained release of different forms of phosphate confers protection against gram-positive and gram-negative pathogens, thereby providing a promising treatment to attenuate expression of tissue-disruptive bacterial phenotypes without eradicating protective flora over the course of intestinal healing.