Proportion of dry eye in type II diabetics.

Introduction: Diabetes mellitus is a multisystem disorder, which is one of the most prevalent and important non-infectious causes of morbidity and mortality worldwide. While diabetic retinopathy (DR) and diabetic cataracts are well-known complications, dry eye syndrome (DES), also referred to as keratoconjunctivitis sicca, is also common in the diabetic population. If left untreated, severe dry eye may lead to eye inflammation, abrasion of the corneal surface, corneal ulcers, and vision loss. So, it is very important to diagnose it earlier as these devastating complications can be prevented. Materials and Methods: A total of 200 adult patients diagnosed with type II diabetes of either sex with an age more than 40 years were selected. Complete ophthalmological examination was done. Dry eye was diagnosed on the basis of various objective tests, and proportion of dry eye and its relation with glycemic control were studied. Conclusion: Patients with uncontrolled type II diabetes had a higher proportion of dry eye disease. A significant co-relation was found among the FBS levels, the HbA1c levels, age, duration of disease, and dry eye in patients with diabetes. No significant co-relation was found between the sex of the patient and dry eye in patients with diabetes. Hence, our study recommends that primary care physicians should advise their patients to get clinical evaluation for dry eye done along with diabetic retinopathy in uncontrolled diabetes.

A Comprehensive Review on Nanoparticles as a Targeted Delivery System for the Treatment of Lung Cancer.

The second most common type of cancer is lung cancer, impacting the human population. Lung cancer is treated with a number of surgical and non-surgical therapies, including radiation, chemotherapy, and photodynamic treatment. However, the bulk of these procedures are costly, difficult, and hostile to patients. Chemotherapy is distinguished by inadequate tumour targeting, low drug solubility, and insufficient drug transport to the tumour site. In order to deal with the issues related to chemotherapy, extensive efforts are underway to develop and investigate various types of nanoparticles, both organic and inorganic, for the treatment of lung cancer. The subject of this review is the advancements in research pertaining to active targeted lung cancer nano-drug delivery systems treatment, with a specific emphasis on receptors or targets. The findings of this study are expected to assist biomedical researchers in utilizing nanoparticles (NPs) as innovative tools for lung cancer treatment, offering new methods for delivering drugs and reliable solid ligands.

Usefulness of Children's Hospital of Philadelphia ROP (CHOP ROP) model in the prediction of type 1 ROP.

Purpose: Children's Hospital of Philadelphia retinopathy of prematurity (CHOP ROP) model can be used to predict ROP, a leading cause of childhood blindness, using risk factors such as postnatal weight gain, birth weight (BW), and gestation age (GA). The purpose of this study was to determine the usefulness of the CHOP ROP for the prediction of treatable ROP. Methods: This was a prospective observational study. Babies <34 weeks of GA, BW <2000 grams, and GA 34-36 weeks with risk factors such as respiratory distress syndrome (RDS) were included; ROP screening, follow-up, and treatment were performed based on national guidelines. The average daily postnatal weight gain was measured, and the CHOP nomogram was plotted. Babies were categorized as high risk or low risk based on the "CHOP" alarm. The sensitivity and specificity of the CHOP ROP for the detection of treatable ROP were determined. In case of poor sensitivity, a new cutoff alarm level was planned using logistic regression analysis. Results: Of 62 screened infants, 23 infants did not fulfill the criteria of the CHOP algorithm and were excluded. Thus, in the study on 39 infants, the predictive model with an alarm level of 0.014 had 100% specificity and 20% sensitivity. With the "new" alarm level (cutoff) of 0.0003, the CHOP nomogram could detect all the infants who developed treatable ROP, that is, sensitivity increased to 100% but specificity decreased to 10.5%. Conclusion: The CHOP ROP model with a cutoff point (0.014) performed poorly in predicting severe ROP in the study. Thus, there is a need to develop inclusive and more sensitive tailor-made algorithms.

Structural Insight on GPR119 Agonist as Potential Therapy for Type II Diabetes: A Comprehensive Review.

Diabetes Mellitus (DM) is a long-term metabolic condition that is characterized by excessive blood glucose. DM is the third most death-causing disease, leading to retinopathy, nephropathy, loss of vision, stroke, and cardiac arrest. Around 90% of the total cases of diabetic patients have Type II Diabetes Mellitus (T2DM). Among various approaches for the treatment of T2DM. G proteincoupled receptors (GPCRs) 119 have been identified as a new pharmacological target. GPR119 is distributed preferentially in the pancreas ß-cells and gastrointestinal tract (enteroendocrine cells) in humans. GPR119 receptor activation elevates the release of incretin hormones such as Glucagon-Like Peptide (GLP1) and Glucose Dependent Insulinotropic Polypeptide (GIP) from intestinal K and L cells. GPR119 receptor agonists stimulate intracellular cAMP production via Gαs coupling to adenylate cyclase. GPR119 has been linked to the control of insulin release by pancreatic ß-cells, as well as the generation of GLP-1 by enteroendocrine cells in the gut, as per in vitro assays. The dual role of the GPR119 receptor agonist in the treatment of T2DM leads to the development of a novel prospective anti-diabetic drug and is thought to have decreased the probability of inducing hypoglycemia. GPR119 receptor agonists exert their effects in one of two ways: either by promoting glucose absorption by ß-cells, or by inhibiting α-cells' ability to produce glucose. In this review, we summarized potential targets for the treatment of T2DM with special reference to GPR119 along with its pharmacological effects, several endogenous as well as exogenous agonists, and its pyrimidine nucleus containing synthetic ligands.

Conformational Flexibility Is a Key Determinant for the Lytic Activity of the Pore-Forming Protein, Cytolysin A.

Several bacterial infections are mediated by pore-forming toxins (PFTs), a subclass of proteins that oligomerize on mammalian cell membranes forming lytic nanopores. Cytolysin A (ClyA), an α-PFT, undergoes a dramatic conformational change restructuring its two membrane-binding motifs (the ß-tongue and the N-terminus helix), during pore formation. A complete molecular picture for this key transition and the driving force behind the secondary structure change upon membrane binding remain elusive. Using all-atom molecular dynamics (MD) simulations of the ClyA monomer and string method based free energy computations with path collective variables, we illustrate that an unfolded ß-tongue motif is an on-pathway intermediate during the transition to the helix-turn-helix motif of the protomer. An aggregate of 28 µs of all-atom thermal unfolding MD simulations of wild-type ClyA and its single point mutants reveal that the membrane-binding motifs of the ClyA protein display high structural flexibility in water. However, point mutations in these motifs lead to a distinct reduction in the flexibility, especially in the ß-tongue, thereby stabilizing the pretransition secondary structure. Resistance to unfolding was further corroborated by MD simulations of the ß-tongue mutant motif in the membrane. Combined with the thermal unfolding simulations, we posit that the ß-tongue as well as N-terminal mutants that lower the tendency to unfold and disorder the ß-tongue are detrimental to pore formation by ClyA and its lytic activity. Erythrocyte turbidity and vesicle leakage assays indeed reveal a loss of activity for the ß-tongue mutant, and delayed kinetics for the N-terminus mutants. On the other hand, a point mutation in the extracellular domain that did not abrogate lytic activity displayed similar unfolding characteristics as the wild type. Thus, attenuation of conformational flexibility in membrane-binding motifs correlates with reduced lytic and leakage activity. Combined with secondary structure changes observed in the membrane bound states, our study shows that the tendency to unfold in the ß-tongue region is a critical step in the conformational transition and bistability of the ClyA protein and mutants that disrupt this tendency reduced pore formation. Overall, our finding suggests that inherent flexibility in the protein could play a wider and hitherto unrecognized role in membrane-mediated conformational transitions of PFTs and other membrane protein transformations.

The Prevention and Therapy of Osteoporosis: A Review on Emerging Trends from Hormonal Therapy to Synthetic Drugs to Plant-Based Bioactives.

Osteoporosis is one of the major health problems worldwide. It is characterized by increased bone fragility and loss of bone matter due to the action of osteoclast cells, which are associated with modified hormone levels and factors such as aging. Bisphosphonates are the primary treatment for osteoporosis. Apart from bisphosphonates, hormone therapy, calcitonin treatment, selective estrogen receptor modulators (SERMs), and strontium ranelate (SR) are some of the other treatments available for osteoporosis. However, these treatments have some side effects, such as oily skin, fluid retention, nausea, long-term toxicity, and even prostate cancer in males, and thus natural therapies that incur fewer side effects are sought. Phytochemicals, antioxidants, and other plant-based bioactives are important in the human diet. They are abundant in fruits and help against various chronic diseases, including bone disorders. Other providers of these important compounds are the medicinal plant parts. In this article, we highlight the various species of plants and herbs that are useful for the treatment of osteoporosis. The prospect of using these plant-based bioactives in amelioration of osteoporosis as an alternative to hormonal and synthetic drug-based therapy is also discussed.

MR tracking of iron-labeled glass radioembolization microspheres during transcatheter delivery to rabbit VX2 liver tumors: feasibility study.

PURPOSE: To prospectively test the hypothesis that iron labeling of radioembolization microspheres permits their visualization by using magnetic resonance (MR) imaging for in vivo tracking during transcatheter delivery to liver tumors. MATERIALS AND METHODS: All experiments were approved by the Institutional Animal Care and Use Committee. Phantom studies were performed to quantify microsphere relaxivity and volume susceptibility properties and compare image contrast patterns resulting from aggregate deposition of unlabeled and iron-labeled microspheres. In seven rabbits in which nine VX2 liver tumors were implanted, T2*-weighted gradient-echo (GRE) MR images with negative image contrast (NC), white-marker (WM) GRE images with positive image contrast (PC), and on-resonance water-suppression turbo spin-echo (SE) images with PC were obtained before and after catheter-directed administration of microspheres into the hepatic artery. During each injection, serial GRE acquisitions were performed for real-time visualization of microsphere delivery. Contrast-to-noise ratios (CNRs) were measured between regions of microsphere accumulation and regions of normal liver parenchyma that demonstrated no apparent microsphere accumulation. Pre- and postinjection CNR measurements at identical spatial positions were compared by using paired t test (alpha = .05). RESULTS: Conventional microspheres did not produce detectable image contrast in phantoms. Iron-labeled microspheres produced susceptibility-induced dipole patterns with spatial extent of image contrast increasing with increasing microsphere dose. Real-time image series depicted both preferential delivery to tumor tissues and nontargeted delivery to adjacent organs. T2*-weighted GRE, WM GRE, and on-resonance water-suppression turbo SE each permitted in vivo visualization of the microsphere deposition, with postinjection CNR values (mean, 14.29 +/- 3.98 [standard deviation], 1.87 +/- 0.93, and 19.30 +/- 8.72, respectively) significantly greater than corresponding preinjection CNR values (mean, 2.02 +/- 4.65, 0.02 +/- 0.27, 0.85 +/- 2.65, respectively) (P < .05). CONCLUSION: Microsphere tracking during radioembolization may permit real-time verification of delivery and detection of extrahepatic shunting.