Mutational analysis of CRYAA gene of cataract and investigating risk assessment factors responsible for eye diseases in district buner, KPK, Pakistan.

This research has been designed to analyze the risk factors of major eye diseases and the genetic alterations contributing to the manifestation of such disease. For this purpose, data was collected from 256 patients diagnosed by an ophthalmologist by using a specialized questionnaire. Blood samples were collected from 100 patients to perform a genetic investigation of cataracts. Whole genomic DNA was extracted from blood samples via the phenol-chloroform method. The purified DNA was used as the template for the amplification of about 400 bp fragments amplifying exons 1 and 2 of the CRYAA gene. The statistical analysis showed that 68% of individuals were blind due to cataracts. During molecular analysis, nucleotide sequences obtained have resulted in one silent mutation that occured at 20 positions in exon 2. It was replacing A>G which in turn substitutes the Lysine at position 70 for Arginine. It was interpreted by statistical analysis that this mutation did not result in a significant change in the CRYAA gene. In addition, protein analysis showed no significant changes in the structure of normal and mutated genes. At last, it is concluded that environmental risk factors play a major role in the studied diseases as compared to genetic factors. It is recommended to extend the study to a larger population to study all exons of the CRYAA gene as well as develop better estimates of the magnitude of the problems of visual loss and eye diseases in the Pakistani population.

Target-based drug repurposing against Candida albicans-A computational modeling, docking, and molecular dynamic simulations study.

The emergence of multidrug-resistant strains of Candida albicans has become a global threat mostly due to co-infection with immune-compromised patients leading to invasive candidiasis. The life-threatening form of the disease can be managed quickly and effectively by drug repurposing. Thus, the study used in silico approaches to evaluate Food and Drug Administration (FDA) approved drugs against three drug targets-TRR1, TOM40, and YHB1. The tertiary structures of three drug targets were modeled, refined, and evaluated for their structural integrity based on PROCHECK, ERRAT, and PROSA. High-throughput virtual screening of FDA-approved drugs (8815), interaction analysis, and energy profiles had revealed that DB01102 (Arbutamine), DB01611 (Hydroxychloroquine), and DB09319 (Carindacillin) exhibited better binding affinity with TRR1, TOM40, and YHB1, respectively. Notably, the molecular dynamic simulation explored that Gln45, Thr119, and Asp288 of TRR1; Thr107 and Ser121 of TOM40; Arg193, Glu213, and Ser228 of YHB1 are crucial residues for stable drug-target interaction. Additionally, it also prioritized Arbutamine-TRR1 as the best drug-target complex based on MM-PBSA (-52.72 kcal/mol), RMSD (2.43 Å), and radius of gyration (-21.49 Å) analysis. In-depth, PCA results supported the findings of molecular dynamic simulations. Interestingly, the conserved region (>70%) among the TRR1 sequences from pathogenic Candida species indicated the effectiveness of Arbutamine against multiple species of Candida as well. Thus, the study dispenses new insight and enriches the understanding of developing an advanced technique to consider potential antifungals against C. albicans. Nonetheless, a detailed experimental validation is needed to investigate the efficacy of Arbutamin against life-threatening candidiasis.

A systematic review on distribution and antifungal resistance pattern of Candida species in the Indian population.

The emergence of antifungal drug resistance in Candida species has led to increased morbidity and mortality in immunocompromised patients. Understanding species distribution and antifungal drug resistance patterns is an essential step for novel drug development. A systematic review was performed addressing this challenge in India with keywords inclusive of 'Candida', 'Antifungal Drug Resistance', 'Candidemia', 'Candidiasis' and 'India'. A total of 106 studies (January 1978-March 2020) from 20 Indian states were included. Of over 11,429 isolates, Candida albicans was the major species accounting for 37.95% of total isolates followed by C. tropicalis (29.40%), C. glabrata (11.68%) and C. parapsilosis (8.36%). Rates of antifungal resistance were highest in non-albicans Candida (NAC) species - C. haemuloni (47.16%), C. krusei (28.99%), C. lipolytica (28.89%) and C. glabrata (20.69%). Approximately 10.34% isolates of C. albicans were observed to be drug resistant. Candida species were frequently resistant to certain azoles (ketoconazole-22.2%, miconazole-22.1% and fluconazole-21.8%). In conclusion, the present systematic review illustrates the overall distribution and antifungal resistance pattern of Candida species among the Indian population that could be helpful in the future for the formation of treatment recommendations for the region but also elsewhere. LAY SUMMARY: A total of 106 studies were reviewed to define the prevalence, distribution and antifungal resistance pattern of Candida species in India. The presented data could become the point of reference for all reported findings on Candida species in India.

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target.

As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.

SAR-CoV-2 infection, emerging new variants and the role of activation induced cytidine deaminase (AID) in lasting immunity.

As the world faces a fourth COVID-19 spike, scientists are learning a lot more about the new SARS-CoV-2 strains that were previously unknown. Currently, the Delta versions of SARS-CoV-2 have become the prevalent strains in much of the world since it first appeared in India in late 2020. Researchers believe they have discovered why Delta has been so successful: those infected with it create significantly more virus than those infected with the original strain of SARS-CoV-2, making it extremely contagious. This has redirected the focus to how our immune system defends us from these various pathogens and initiates such varied responses. Hundreds of research papers have been published on the origins of long-lasting immune responses and disparities in the numbers of different immune cell types in COVID 19 survivors, but the primary architect of these discrepancies has yet to be discovered. In this essay, we will concentrate on the primary architect protein, activation induced cytidine deaminase (AID), which triggers molecular processes that allow our immune system to produce powerful antibodies and SARS-CoV-2 specific B cells, allowing us to outwit the virus. We believe that if we ever achieve permanent immunity to SARS-CoV-2 infection, AID will be the key to releasing it.

Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans.

Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural compounds in this context represent promising alternatives having potential to be exploited for improving human health. The present study was therefore designed to evaluate the antifungal effect of a naturally occurring phenolic, octyl gallate (OG), on Candida albicans and to investigate the underlying mechanisms involved. We demonstrated that OG at 25 µg/ml could effectively inhibit C. albicans. Mechanistic insights revealed that OG affects mitochondrial functioning as Candida cells exposed to OG did not grow on non-fermentable carbon sources. Dysfunctional mitochondria triggered generation of reactive oxygen species (ROS), which led to membrane damage mediated by lipid peroxidation. We explored that OG inhibited glucose-induced reduction in external pH and causes decrement in ergosterol levels by 45%. Furthermore, OG impedes the metabolic flexibility of C. albicans by inhibiting the glyoxylate enzyme isocitrate lyase, which was also confirmed by docking analysis. Additionally, OG affected virulence traits such as morphological transition and cell adherence. Furthermore, we depicted that OG not only prevented biofilm formation but eliminates the preformed biofilms. In vivo studies with Caenorhabditis elegans nematode model confirmed that OG could enhance the survival of C. elegans after infection with Candida. Toxicity assay using red blood cells showed only 27.5% haemolytic activity. Taken together, OG is a potent inhibitor of C. albicans that warrants further structural optimization and pharmacological investigations.

COVID-19 pandemic: Mechanistic approaches and gender vulnerabilities.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19), a severe respiratory damaging syndrome with serious health complications worldwide. SARS-CoV-2 was unfamilar before the epidemic started in Wuhan, China, in December 2019. COVID-19 is currently a pandemic influencing several countries worldwide. One of the mysteries of the new coronavirus is that it is deadlier for men than women with the male mortality rate is twice as high as that of females.

Impact of length of replication competent genome of hepatitis B virus over the differential antigenic secretion.

Hepatitis B virus (HBV) genome consists of circular partially double stranded DNA of 3.2 kb size which gets converted into covalently closed circular DNA (cccDNA) during its life cycle. It then acts as a template for formation of pregenomicRNA (pgRNA) of 3.5 kb. Absence of appropriate animal models prompted a need to establish a better in vitro culture system to uncover the propagation and survival mechanisms of the virus. There is scarcity of data to represent the significance of varying length of replication competent viral genome on the secretion of viral secretory proteins/antigens and in turn on the overall effects on the accomplishment of the viral life cycle. The present study was undertaken to ascertain a suitable replication competent construct in which the viral life cycle of HBV with varying clinical relevance can be studied efficiently. Two constructs (pHBV 1.3 and pHBV 1X) of different sizes were used to transfect hepatoma cells and consequently the secretory antigens were monitored. In vector free approach (pHBV 1X), 3.2 kb viral DNA is directly transfected in the culture system whereas in vector mediated approach more than full length of viral genome is cloned in a vector (pHBV 1.3X) and transfected to obtain a 3.5 kb pgRNA intermediate. HBV secretes two important antigens; HBsAg and HBeAg. HBsAg is a hallmark of infection and is the first to be secreted in the blood stream whereas HBeAg is a secretory protein and remains associated with the viral replication. The construct pHBV 1.3X referring to as more than full length, by virtue of being capable of undergoing transcription without the synthesis of cccDNA intermediate (unlike the clinical situation where an intermediate step of cccDNA synthesis is an essential component to initiate the viral life cycle) appears to be better system for studying viral life cycle in in vitro culture system. The reasons could be assigned to the fact that as low as 100 ng of viral DNA was shown to quantify the replicative phenotypes with this construct. The better efficiency of this construct at prima facie, appears to be mediated through the significantly higher levels of pgRNA transcript during the viral life cycle.

STAT6 variants and non-atopic asthma in Pakistani population.

Asthma a chronic airway inflammatory disease mainly characterized by airways obstruction. Airway hyper responsiveness particularly in eosinophils and inflammatory mediators affect the bronchial mucosa. Genetic association studies show the association of single nucleotide polymorphisms (SNPs) in the STAT6 gene with asthma risk. Role of Signal transducer and activator of transcription 6 (STAT6) is acute for T-helper 2 (Th2) mediated responses during allergic airway diseases. Objective was to investigate whether the two single nucleotide polymorphism (rs4559 and rs324011) in STAT6 gene are associated with non-atopic asthma risk in Pakistani population. One hundred (100) asthma patients with a positive family history with at least one-first degree asthma affected relative were enrolled. Normal healthy individuals (n=100) were also included as control subjects in the current study. STAT6 SNPs rs4559 and rs324011 were genotyped using SNaPSHOT mini-sequencing assay and the obtained data was statistically analyzed by online SHEsis software. A case-control study for association of STAT6 polymorphisms rs4559 and rs324011 with asthma risk was performed. The SNP rs4559 was found statistically significantly associated with increased susceptibility of developing non-atopic asthma in Pakistani individuals. The SNP rs324011 polymorphism in intron 2 of STAT6 gene may be associated with increased susceptibility of the development of non-atopic asthma as a strong statistically significant difference in allele frequency and genotype was observed between asthmatics and controls showing association with non-atopic asthma in Pakistani individuals. rs4559 and rs324011SNPs in STAT6 found associated with non-atopic asthma risk. We observed the statistically significant association between STAT6 polymorphisms with intrinsic (non-atopic) asthma in Pakistani population.

Eugenol and carvone as relaxants of arsenic and mercury hypercontracted rat trachea.

Exposure to arsenic and mercury is known to cause respiratory problems in both humans and animals. In this study, we elicit and compare maximum contraction caused by As(III) and Hg(II) when the pollutants are fully equilibrated with contractile machinery in resting mode. Hypercontraction of 27% and 69% was obtained following exposure of tracheal rings to 25 µM As(III) and 6 nM Hg(II) for 40 min, respectively. Co-incubation of tracheal rings with pollutants and verapamil, sodium nitroprusside or apocynin indicates that major contributors to As(III) and Hg(II) caused hypercontraction are reactive oxygen species (ROS) elevation and nitric oxide (NO) depletion. Changes in calcium influx have minor contribution in As(III) and Hg(II) caused increased contraction of tracheal tissues. Eugenol and carvone caused relaxation of 38% and 45% in pollutant unexposed rings, 56% and 49% in As(III)-exposed tracheal rings, and 54% and 47% in Hg(II)-exposed tracheal rings. Pathway delineation studies indicate that the major effect of eugenol originates from quenching of ROS whereas that of carvone originates from the blockage of extracellular calcium influx. Both molecules also show a minor stimulatory effect on NO generation. In line with their suggested mode of relaxation, eugenol is found to better ameliorate both As(III)- and Hg(II)-caused hypercontraction. Carvone, though a better relaxant than eugenol, comes out as poor ameliorator of both As(III)- and Hg(II)-caused hypercontraction, as the pathway on which it acts is not elevated following exposure to these pollutants.

Effect of two monoterpene phenols on antioxidant defense system in Candida albicans.

Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms. This study evaluates the antioxidant defense response to lower concentrations of thymol and carvacrol in Candida albicans. The antioxidant defense responses in C. albicans are important for developmental mechanisms pertaining to resistance against the immune system, infection establishment and drug resistance. In this view, primary and secondary antioxidant defense enzymes, and oxidative stress markers including glutathione and lipid peroxidation were determined in C. albicans cells exposed to lower concentrations of thymol and carvacrol. These compounds were found to induce oxidative stress and compromised the antioxidant defense system in C. albicans at lower concentrations. This study helps in understanding the 'in cell' antifungal mechanisms of natural monoterpene phenols originating from oxidative stress. Thymol and carvacrol induced membrane deterioration reported earlier, is further explained as a result of a toxic radical cascade mediated by lipid peroxidation. Findings reinforce the observed toxic oxidizing effects of these compounds as a consequence of direct damage to antioxidant components and not to their genetic manipulations.

Increased A3AR-dependent vasoconstriction in diabetic mice is promoted by myeloperoxidase.

Vascular dysfunction importantly contributes to mortality and morbidity in various cardiac and metabolic diseases. Among endogenous molecules regulating vascular tone is adenosine, with the adenosine A3 receptor (A3AR) exerting cardioprotective properties in ischemia and reperfusion. However, overexpression of A3AR is suggested to result in vascular dysfunction and inflammation. The leukocyte enzyme myeloperoxidase (MPO) is an important modulator of vascular function with nitric oxide-consuming and proinflammatory properties. Increased MPO plasma levels are observed in patients with cardiovascular disorders like heart failure, acute coronary syndromes, and arrhythmias. Given that vascular dysfunction and inflammation are also hallmarks of diabetes, the role of MPO in adenosine-dependent vasomotor function was investigated in a murine model of diabetes mellitus. Wild-type (WT) and MPO-deficient (Mpo) mice were treated with Streptozotocin (STZ), which induced an increase of MPO plasma levels in WT mice and led to enhanced aortic superoxide generation as assessed by dihydroethidium staining in STZ-treated WT mice as compared with controls. The vasoconstriction of aortic segments in response to the A3AR agonist Cl-IB-MECA (2-Chloro-N6-(3-iodobenzyl)-N-methyl-5-carbamoyladenosine) as determined by isometric force measurements was augmented in diabetic WT as compared with diabetic Mpo mice. Moreover, A3AR protein expression was enhanced in STZ-treated mice but was attenuated by MPO deficiency. The current data reveal an MPO-mediated increase of vascular A3AR expression under diabetic conditions, which leads to enhanced vasoconstriction in response to A3AR agonists and discloses an additional mechanism of MPO-mediated vascular dysfunction.

Biocompatible carbon quantum dots as versatile imaging nanotrackers of fungal pathogen - Candida albicans.

Aim: The development of carbon quantum dots (C-QDs) as nanotrackers to understand drug-pathogen interactions, virulence and multidrug resistance. Methods: Microwave synthesis of C-QDs was performed using citric acid and polyethylene glycol. Further, in vitro toxicity was evaluated and imaging applications were demonstrated in Candida albicans isolates. Results: Well-dispersed, ultra small C-QDs exhibited no cyto/microbial/reactive oxygen species-mediated toxicity and internalized effectively in Candida yeast and hyphal cells. C-QDs were employed for confocal imaging of drug-sensitive and -resistant cells, and a study of the yeast-to-hyphal transition using atomic force microscopy in Candida was conducted for the first time. Conclusion: These biocompatible C-QDs have promising potential as next-generation nanotrackers for in vitro and in vivo targeted cellular and live imaging, after functionalization with biomolecules and drugs.

Scientists have used radiolabeled drugs and radioactive tracking agents for the imaging and study of drug resistance in microbial pathogens. But, these radiolabeled drugs or radiotrackers pose health hazards and environmental risks. However, such limitations can be overcome by designing nontoxic, environment-friendly, nanotechnology-based fluorescent imaging agents. This study demonstrates the development and application of cost-effective, nontoxic carbon-based quantum dots for imaging of drug-sensitive and -resistant microbial strains and transition to different morphological forms (yeast-to-hyphae transition) in fungal pathogens. The results demonstrated the suitability of carbon quantum dots as next-generation nano-based bioimaging/tracking agents for cellular imaging. The availability of such nontoxic fluorescent tracking agents is likely to offer promising solutions in therapeutics and diagnostics by providing insight into various mechanisms and functional links related to drug resistance, virulence and pathogenicity.

Passivity-based Rieman Liouville fractional order sliding mode control of three phase inverter in a grid-connected photovoltaic system.

Photovoltaic (PV) system parameters are always non-linear due to variable environmental conditions. The Maximum power point tracking (MPPT) is difficult under multiple uncertainties, disruptions and the occurrence of time-varying stochastic conditions. Therefore, Passivity based Fractional order Sliding-Mode controller (PBSMC) is proposed to examine and develop a storage function in error tracking for PV power and direct voltage in this research work. A unique sliding surface for Fractional Order Sliding Mode Control (FOSMC) framework is proposed and its stability and finite time convergence is proved by implementing Lyapunov stability method. An additional input of sliding mode control (SMC) is also added to a passive system to boost the controller performance by removing the rapid uncertainties and disturbances. Therefore, PBSMC, along with globally consistent control efficiency under varying operating conditions is implemented with enhanced system damping and substantial robustness. The novelty of the proposed technique lies in a unique sliding surface for FOSMC framework based on Riemann Liouville (R-L) fractional calculus. Results have shown that the proposed control technique reduces the tracking error in PV output power, under variable irradiance conditions, by 81%, compared to fractional order proportional integral derivative (FOPID) controller. It is reduced by 39%, when compared to passivity based control (PBC) and 28%, when compared to passivity based FOPID (EPBFOPID). The proposed technique led to the least total harmonic distortion in the grid side voltage and current. The tracking time of PV output power is 0.025 seconds in PBSMC under varying solar irradiance, however FOPID, PBC, EPBFOPID, have failed to converge fully. Similarly the dc link voltage has tracked the reference voltage in 0.05 seconds however the rest of the methods either could not converge, or converged after significant amount of time. During solar irradiance and temperature change, the photovoltaic output power has converged in 0.018 seconds using PBSMC, however remaining methods failed to converge or track fully and the dc link voltage has minimum tracking error due to PBSMC as compared to the other methods. Furthermore, the photovoltaic output power converges to the reference power in 0.1 seconds in power grid voltage drop, whereas other methods failed to converge fully. In addition power is also injected from the PV inverter into the grid at unity power factor.

Comparison of Partial Meniscectomy With Meniscal Repair With Respect to Functional Outcome.

Introduction Meniscus tear is a commonly encountered sports-related injury requiring surgical intervention due to knee mobility dysfunction and discomfort. Previously, it has been thought that these are non-functional vestigial structures and they used to be excised commonly. Recent studies have shown that meniscal repair gives superior results when compared with partial meniscectomy. Methods This quasi-experimental study was conducted at the Orthopedics Department, Khyber Teaching Hospital, Peshawar, Pakistan. A total of 92 patients of both genders with meniscal injuries were included. Forty-six of them underwent meniscal repair (Group A), and 46 underwent partial meniscectomy (Group B). Functional outcome was noted after 12 weeks and recorded. Results The age range was from 18 to 50 years with a mean of 28.630±6.64 years in Group A and 29.630±8.12 years in Group B. Functional outcome was excellent in 44 (95.7%) patients who underwent meniscal repair as compared to 23 (50%) patients who underwent partial meniscectomy (P= 0.000). Conclusion It is concluded that meniscal repair should be pursued over partial meniscectomy when surgically treating meniscal tears.

Surgical Strategies for Ingrown Toenails: A Comprehensive Review of Techniques, Outcomes, and Advancements.

Ingrown toenail (IGTN), known as onychocryptosis or unguis incarnatus, is a painful condition affecting the big toe, with symptoms including pain, inflammation, and infection. This review explores surgical options for IGTN, categorized into altering the nail plate or diminishing periungual tissues. Conservative treatments alleviate early-stage symptoms, while surgical interventions are reserved for severe cases. Various surgical techniques are discussed, such as the Winograd technique, Vandenbos procedure, chemical matricectomy, radiofrequency ablation, bipolar diathermy, carbon dioxide laser ablation, Zadik's procedure, Howard-Dubois procedure, Super U procedure, Noël's procedure, knot technique, and toenail paronychium flap. The choice of procedure depends on the severity and recurrence of IGTN.

Spectroscopic investigations on fungal aspartic protease as target of gallic acid.

Proteases are a major virulence factor in pathogenic fungi and can serve as a potential therapeutic target. The interaction of gallic acid (GA) with Aspartic fungal protease (PepA) was investigated using biophysical and in silico approaches. UV-Vis and fluorescence spectroscopy showed complex formation and static quenching of PepA by GA with Ka of 7.4 × 105 M-1 and stoichiometric binding site (n) of 1.67. CD-spectroscopy showed marked changes in helical content and synchronous fluorescence spectra measurements indicated significant changes in the microenvironment around tryptophan residues in the GA-PepA complex. Outcomes of Isothermal Titration Calorimetry (ITC) measurement and molecular modelling studies validated the spectroscopic results. The binding of GA to Human Serum albumin (HSA) was moderate (Ka = 1.9 × 103 M-1) and did not cause structural disruption of HSA. To conclude, gallic acid is strongly bound to fungal protease leading to structural disruption and inhibition whereas HSA structure was largely conserved. Gallic acid thus appears to be a potential therapeutic agent against fungal proteases.

Aberrations in the progesterone pathway and the Th1/Th2 cytokine dichotomy - An evaluation of RPL predisposition in the northeast Indian population.

PROBLEM: Recurrent pregnancy loss (RPL) is the spontaneous loss of two or more consecutive pregnancies prior to 20 weeks of gestation, occurring in 1% of the reproductive-age population. It is a major cause of infertility in India with a staggering 7.46% prevalence rate. METHOD OF STUDY: Blood and product of conception (POCs) from RPL cases (n = 65) were enrolled for this study, along with cases of medically terminated pregnancy (MTP, n = 80) and term delivery cases (n = 90) as control. ELISA for progesterone and progesterone induced blocking factor (PIBF) levels was carried out, followed by mRNA expression analysis of progesterone receptor isoform B (PR-B) and its downstream immunomodulatory effectors, namely, PIBF, IL-10 and IL-12. Screening of PROGINS haplotype of PR gene and PIBF polymorphism were also conducted to correlate with their respective gene expression profiles. RESULTS: Serum progesterone level was found to be comparable in the RPL and MTP cases. Although the mRNA expression of PR-B was found to be downregulated in the RPL cases, no significant PROGINS haplotype was observed. Presence of a single nucleotide polymorphism (SNP) in the PIBF gene (rs1372000) was more in healthy controls compared to RPL cases. Serum PIBF levels were found to be lower in the RPL cases with a resultant increase in IL-12 and a decrease in IL-10 mRNA expression in these cases. CONCLUSIONS: This study indicates that progesterone, acting through PIBF, modulates the immunological state of pregnancy to be Th1-biased in RPL, indicative of a pro-inflammatory, labour-like state not desired for a healthy pregnancy.

Enhancing Documentation Precision in Ophthalmic Surgery: A Quality Improvement Project.

Background Effective clinical documentation, particularly operative notes, is essential for maintaining healthcare standards and fostering interdisciplinary communication. This study focuses on improving the quality of ophthalmic operative notes by adopting the Royal College of Surgeons (RCS) guidelines for good surgical practice. Methodology A retrospective cross-sectional audit at Khyber Teaching Hospital, Pakistan, assessed 138 operative notes against the RCS criteria. After an educational session and the placement of memory aids in operation theaters, a re-audit of 125 notes was conducted. Parameters were selectively applied based on relevance to specific cases, and omissions were discussed with the local ethical committee. Results The initial audit revealed deficiencies in 10 critical areas, with only three parameters exceeding 85% accuracy. The re-audit showed significant improvement across these parameters, achieving documentation of 85.3% of all criteria. Paired t-test results indicated a substantial difference in documentation quality before and after interventions. Conclusions A combined strategy involving surgeon education, memory aids, and adherence to established standards significantly enhances operative note quality. The study underscores the importance of sustained reinforcement mechanisms for continuous improvements in documentation practices.

Cinnamic aldehydes affect hydrolytic enzyme secretion and morphogenesis in oral Candida isolates.

Effect of cinnamaldehyde (CD), 4-hydroxy-3-methoxy cinnamaldehyde (HMCD) and 3,5-dimethoxy-4-hydroxy cinnamaldehyde (HDMCD) on growth and virulence factors of standard (Candida albicans 90028) and 26 oral isolates of C. albicans has been investigated. Growth was significantly inhibited by all three compounds in both solid and liquid medium, no systematic difference was observed between various isolates. MIC90 ranged from 125 to 450 µg/ml for CD, 100-250 µg/ml for HMCD and 62.5-125 µg/ml for HDMCD. All oral isolates were found to be proteinase and phospholipase secretors, both proteinase and phospholipase secretion was significantly inhibited by all the three tested molecules. No systematic difference in secretion or its inhibition was observed between standard and oral isolates as also between various isolates. Average drop in proteinase and phospholipase secretion caused by ½ MIC of CD was 33% and 28%, HMCD; 46% and 44%, HDMCD; 59% and 54%. The standard strain and all the 26 oral isolates displayed morphogenesis under triggering experimental conditions; no difference was seen between standard and various isolates. In the absence of test compounds hyphae development at 300 min was 83% for standard strain whereas average hyphae development for oral isolates was 85%. Average hyphal transition was suppressed by all tested compounds. At ½ MIC concentration at 300 min average hyphal transition of standard and oral isolates was CD; 49% and 57%, HMCD; 45% and 38%, HDMCD; 5% and 5%. Average haemolytic activity of the three tested compounds varied from 10 to 15% at their highest MIC compared to 20% shown by fluconazole at typical MIC of 30 µg/ml.