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Whole pharmaceutical areas needed various innovative and scientific solutions to solve the current problems related to cGMP practices, production, documentation, regulatory body requirements (USFDA, WHO, EU-GMP, PICS), quality of product, etc. To overcome such problems, different computer system software plays an important role by monitoring and maintaining the current practices of the pharma industry. Installing such software will help the pharma industry to improve their cGMP practices and fulfillment the regulatory body’s requirements. This article gives overview on different types of software used in the pharmaceutical industry and hospitals. It also covers importance and their need in the pharma industry, as well as the meaning of software used in hospitals.

Seasonal and occupational exposure of the human body to extreme cold temperatures can result in cell death in the exposed area due to the formation of ice crystals. This leads to superficial or deep burn injury and compromised functionality. Currently available therapeutics can be ineffective in extreme cases, and thus, it is necessary to develop prophylactic strategies. In this study, we have devised a combination of known synthetic cryopreservative agents (termed SynAFP) and evaluated their potential antifreeze applications on skin. The prophylactic activity of SynAFP in vitro is indicated by improved cellular revival and cell viability, retention of the cytoskeleton, and normal cell cycle progression even after cold stress. A comprehensive whole-cell proteomic approach revealed that in the presence of SynAFP, cold-induced downregulation of proteins involved in cell-cell adhesion and upregulation of those related to mitochondrial stress were ameliorated. Pre-application of SynAFP in mice facing a frostbite challenge prevents their skin from incurring significant injury as confirmed through macroscopic and histological examination. Moreover, multiple applications of SynAFP on mouse skin at room temperature did not compromise skin integrity. SynAFP was also formulated in an

Background Invasive Mold Infections (IMI) cause significant morbidity and mortality, particularly in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT) recipients. Although the risk has significantly decreased with the use of triazole agents as primary prophylaxis, breakthrough infections still occur. Risk factors for IMI have been well-described. Limited data exist on factors predicting mortality. Methods We identified cases using the Cancer registry and Microbiology data at Mayo Clinic Minnesota from 11/19/2011–8/6/2021 and Mayo Clinic Arizona and Florida from 09/13/2017–11/19/2021. We conducted a retrospective review to identify cases of proven/probable IMI per EORTC/MSG criteria. Patients who received at least 7 days of anti-mold prophylaxis were considered having breakthrough infection (Br-IMI). Survival function was estimated using the Kaplan-Meier method. We evaluated predictors of mortality using Cox regression analysis. Results 401 cases of IMI were included (80.2% aspergillosis, 10.2% fusariosis, 8.4% mucormycosis, 1.2% scedosporiosis). 189 patients had proven/probable and 212 had possible disease. 12-week mortality for the entire cohort was 33%. There were 87 cases of Br-IMI (21.6%) on mold-active prophylaxis (posaconazole n=54, voriconazole n=26, isavuconazole n=5, itraconazole n=1, liposomal amphotericin B n=1). A comparison between patients not receiving prophylaxis and those with Br-IMI is shown in Table 1. Higher proportion of patients with Br-IMI had prolonged neutropenia/lymphopenia and graft-versus-host disease involving the gastrointestinal tract or lungs. Positive Aspergillus galactomannan (index ≥ 1.0) was seen more in patients who were not on mold-active prophylaxis. Mortality was 31.5% in patients not receiving prophylaxis and 41.3% with Br-IMI (Figure 1). In multivariate analysis, age, prolonged neutropenia, active HM, Br-IMI and HSCT were associated with increased mortality (Table 2). Conclusion In this cohort, the rate of Br-IMI was significant despite the use of primary prophylaxis (mainly posaconazole). Mortality was higher in patients with Br-IMI compared to those not receiving mold-active prophylaxis. Therefore, clinicians should remain alert to the possibility of Br-IMI. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support.

Highlights • Compared to those treated with subcutaneous therapy, patients with COVID-19 treated intravenous tocilizumab has improved measurements in respiratory parameters seven days following therapy. • Patients that received intravenous therapy were more likely to survive hospitalization. • Laboratory markers of inflammation did not predict clinical response to tocilizumab therapy., Background The release of pro-inflammatory cytokines, resulting in cytokine storm syndrome, contributes to the morbidity and mortality associated with COVID-19 disease. This study aimed to compare the effects of intravenous (IV) and subcutaneous (SC) tocilizumab, an IL-6 receptor antagonist, on respiratory parameters and clinical outcome in patients with COVID 19. Methods We performed a retrospective cohort study of hospitalized patients with COVID-19 treated with either IV or SC tocilizumab from March 26, 2020 to May 18, 2020. Respiratory parameters seven days after receiving tocilizumab therapy were compared to baseline measurements. All patients were assessed until discharged from the hospital. Results Tocilizumab was administered to 125 patients: 65 received IV and 60 received SC therapy. At day seven, 52% of the patients in the IV group demonstrated improvement in respiratory parameters, compared to 28% in the SC group (P = 0.01). Mortality rates at days seven and 28 were 15% and 37%, respectively in the IV group and 17% and 50%, respectively in the SC group (P = NS). In-hospital mortality rate was 38% for the IV group versus 57% for the SC group (P = 0.04). More than 90% of patients in each group received corticosteroids, however significantly more patients in received convalescent plasma in the IV group. Conclusions At the doses used in this study, IV tocilizumab is preferred over SC therapy for the treatment of cytokine storm syndrome due to COVID-19.

To compare Multiphase CT Angiography derived source images (mCTA-SI) in acute ischemic stroke (AIS) with CT Perfusion (CTP) derived automated color maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) and to assess the comparability of mCTA-SI with CTP in the prediction of final radiological and clinical outcome.This prospective single-centre observational study comprised of patients with AIS of the anterior circulation, presenting within 24 h and undergoing neuroimaging under stroke protocol with follow-up. Non-contrast computed tomography (NCCT), mCTA, and CTP were acquired with follow-up NCCT at 24 h and modified Rankin score (mRS) at 3 months. mCTA-SI and CTP color maps were scored by the ASPECTS (Alberta Stroke program early CT score) method and compared amongst each other and with the outcome. ROC (Receiver operating characteristic) curves were plotted considering mRS 0-2 and FIV≤ 28 ml as favourable clinical and radiological outcomes respectively.The study included 55 patients. The 1st and 2nd phase of mCTA-SI correlated significantly with CBF maps (r = 0.845, p 0.01, r = 0.842, p 0.01 respectively). 3rd phase of mCTA-SI correlated significantly with CBV maps (r = 0.904, p 0.01). A favourable functional and radiological outcome was best predicted by the 1st (AUC 0.8, 95%CI 0.671-0.896) and 2nd ( AUC 0.895, 95% CI 0.783-0.962The 1st and 2nd phases of mCTA-SI produces results congruent to CBF color maps and the 3rd phase of mCTA-SI simulate CBV color maps. In addition to predicting radiological and functional outcomes, mCTA can predict the salvageable and non-salvageable tissue in AIS and is non-inferior to CTP.

Objective: This study aimed to compare the unstimulated salivary estrogen levels in postmenopausal women with and without oral dryness. Methodology: A study was carried out on 70 selected postmenopausal women, out of which 35 were in the case group and 35 were in the control group. A questionnaire related to oral dryness was given to all the patients to evaluate their response to oral dryness. Patients were asked to spit in a plastic container, and their unstimulated saliva samples were obtained and analyzed for estimation of salivary estrogen levels by ELISA technique. After analyzing the results of salivary estrogen levels, the patients in the case group with low levels of estrogen were subjected to HRT under the guidance of a gynecologist. The patients were followed after 3 months of therapy for their response to oral dryness by the questionnaire, and salivary estrogen levels were again reevaluated after the therapy. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, version 15.0 for windows). The Pearson’s correlation and Student’s unpaired t-test were used for comparisons. Results: Before hormone replacement therapy, the mean estrogen level of the case group was 1.0031, and the mean estrogen level of the control group was 4.0080 pg/ml. This suggested that the reduced levels of estrogen hormone after menopause were associated with the complaint of oral dryness in these females. The mean salivary estrogen levels in the case group after HRT were more than the levels before HRT. Conclusion: Estrogen levels were reduced in patients with oral dryness. Further, the patients receiving HRT showed significant improvement in symptoms of oral dryness.

The ratio of protein to creatinine (PCR) in urine is a measure of kidney health of a human body. We report the development of a point-of-care (POC) kidney function test (KFT) kit, which is composed of a paper-based PCR sensor, an opto-electrochemical measurement unit, a display, and a facility to transfer data to a smartphone. For the total protein sensor, the pieces of filter papers were coated with a mixture of alcoholic bromophenol blue and citric buffer leading to a chrome-yellow coloration. While for the creatinine sensor the papers were coated with alkaline picrate solution leading to a lemon-yellow coloration of the surface. Dispensing protein (creatinine) solution of known concentration on the respective sensors led to the conversion of chrome-yellow to bluish-green coloration (lemon-yellow to orange coloration) for the total protein (creatinine) sensor. The intensity of such colorations varied with the concentration of the analytes in the solutions. The variations in the intensities of colors with analyte concentration were quantified by integrating a light emitting diode (LED) at one side of each sensor and a light intensity sensor (LIS) on the other side. The intensity of the transmitted rays, passing through the sensors, was found to vary the electrical output of the LIS monotonically with the loading of the total protein or creatinine in the analyte. This helped in obtaining the calibration plots for the PCR sensors. Further, the sensors were employed for the on-spot detection of the unknown PCR in the real human urine samples.

The COVID-19 pandemic has challenged clinicians to recognize COVID-19 as one of the diagnostic explanation for common presentations, including fever, cough, and shortness of breath. Latent tuberculosis is responsible for 80% of active tuberculosis cases in the United States, and presentation can vary from asymptomatic to disseminated disease. This potential diagnosis should be thoroughly investigated in foreign-born patients in US hospitals, regardless of travel history and presenting symptoms. We report a patient diagnosed with postpartum disseminated tuberculosis with hematogenous spread to the fetus.

Breast cancer is the most prevalent cancer known worldwide in women. It is a heterogeneous, phenotypically diverse disease composed of several biologic subtypes that have distinct behavior and response to therapy. Hormone receptor-positive (i.e., estrogen [ER] and/or progesterone [PR] receptor-positive) breast cancers comprise the most common types of breast cancer, accounting for 75% of all cases. This makes endocrine therapy the standardized treatment for patients with ER+/PR+ breast cancer. Drugs that block estrogen receptors or that lower estrogen levels are the mainstay of treatment. High-risk patients benefit from the addition of ovarian function suppression (OFS)/ablation to either an aromatase inhibitor (AI) or tamoxifen. This case report discusses a 36-year-old premenopausal female who presented with an abnormal right breast lump in the upper outer quadrant of the right breast. Due to high suspicion of malignancy, a biopsy was performed which showed features of both lobular and ductal carcinoma with ER and PR positivity, HER 2 was negative. The patient underwent mastectomy with axillary lymph node removal due to concern for multifocal disease. No clinically relevant genetic mutations were present. Oncotype DX breast recurrence score was 16 and no chemotherapy was offered. Due to large tumor size, young age OFS with goserelin 3.6mg/28 days and letrozole 2.5 mg once daily was recommended. After 16 months of treatment, the patient developed a failure of goserelin-induced ovarian suppression. This case report highlights the possibility of the development of hormonal resistance after long-term use of goserelin.

Aanchal Gupta, Roshan Jonash Raymond Barts and The London School of Medicine and Dentistry, London, UKCorrespondence: Aanchal GuptaBarts and The London School of Medicine and Dentistry, Garrod Building, Turner Street, Whitechapel, London, E1 2AD, UKTel +44 7946769695Email a.gupta@smd16.qmul.ac.uk View the original paper by Professor Nguyen and colleagues

Aanchal Gupta, Roshan Jonash Raymond Barts and The London School of Medicine and Dentistry, London, UKCorrespondence: Aanchal GuptaBarts and The London School of Medicine and Dentistry, Garrod Building, Turner Street, Whitechapel, London, E1 2AD, UKTel +44 7946769695Email a.gupta@smd16.qmul.ac.uk View the original paper by Dr Butcher and colleagues

Objectives Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. Methods In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03–8 mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. Results There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired β-lactamase activity also could not explain the range in cefiderocol susceptibility. Conclusions The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.

Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.

BACKGROUND AND PURPOSE : Rhino-orbital-cerebral mucormycosis has emerged as a major opportunistic infection in patients with COVID-19. High clinical suspicion and prompt imaging are crucial for early diagnosis and management. Our study evaluates imaging characteristics of patients with COVID-19 associated Rhino-orbital-cerebral Mucormycosis (CA-ROCM) in a tertiary care hospital in India. MATERIALS AND METHODS : A retrospective analysis of clinical and imaging data of patients with CA-ROCM who presented between December 2020 to June 2021 was performed. All patients had microbiologically or histologically proven sino-nasal mucormycosis along with documented SARS-CoV-2 positive RT-PCR test and/or classical lung imaging features of COVID-19 infection. The extent of sinus involvement, bony erosions, extra-sinus soft tissue extension, orbital-intracranial invasion, perineural spread, and vascular complications were assessed. RESULTS : Fifty patients were included for the final analysis. Diabetes was the most common associated comorbidity. Seven patients presented with stage I disease, 18 patients with stage II, and 25 patients with stage III disease. The stage of disease showed a positive statistical correlation with HbA1c levels using Pearson's correlation. The common imaging features were “Black turbinate sign” and non-enhancing sino-nasal mucosa (82%), orbital involvement (76%), and diffusion restriction in the optic nerve (24%). Intracranial involvement was seen as perineural extension into the brain (42%), cerebritis (30%), and internal carotid artery involvement (16%). CONCLUSIONS : CA-ROCM is an acute invasive fungal sinusitis with an aggressive clinical course. Black-turbinate sign and peri-antral soft tissue infiltration are early features, whereas extra-nasal tissue infarction, optic nerve diffusion restriction, and vascular invasion are seen with advanced disease.

Summary Aim To determine the prevalence of hepatic steatosis and fibrosis in patients with T2DM from North India. Research design and methods In this cross-sectional study, Asian Indian patients with T2DM (n,250) underwent liver ultrasonography (USG), Fibroscan for assessment of hepatic steatosis (Controlled Attenuation Parameter, CAP) and hepatic fibrosis (Kilopascals, kPa) respectively. Pearson's correlation analysis & logistic regression analysis for significant predictors of hepatic steatosis and fibrosis were done. The cut-off value of liver span was calculated by ROC-AUC analysis. Results Grade 3 hepatic steatosis was seen in 213 T2DM patients (85.2%). It was higher in males than females and in those with high BMI values. Any degree of fibrosis and severe fibrosis were seen in 205 (62%) and 46 (18.4%) patients, respectively; these were higher in males, specifically in those with BMI >30 kg/m2, and diabetes of a duration more than 5 years. BMI and SGPT were the significant predictors of hepatic steatosis. An increase of 1 unit of BMI above 23 kg/m2 led to 19.6 times increased risk of hepatic steatosis in T2DM patients aged 50 years and above. SGOT and GGTP were significant predictors of any degree of hepatic fibrosis. On ROC-AUC analysis, liver span cut-off values of ≥16.4 cms and ≥16.8 cm in males and females respectively, were predictive of hepatic fibrosis. Conclusion High prevalence of grade 3 hepatic steatosis and hepatic fibrosis needs increased vigilance and corrective lifestyle and pharmacological measures. Asian Indian patients with T2DM and BMI >30 kg/m2, with duration of diabetes above 5 years & an ultrasound derived liver span ≥16.4 cms, should be further evaluated for hepatic fibrosis.

Background Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC. Methods In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echocardiogram and was defined by a new-onset decline in left ventricular ejection fraction (LVEF) of up to 50% or a decline of at least 10% in LVEF relative to baseline in patients with a history of heart failure with reduced EF. Multivariable logistic regression analysis was performed using the R software program (R Foundation for Statistical Computing). Results Of the 359 patients in the final analysis, 19 (5.3%) had SIC, and eight (42.1%) of these 19 patients and 60 (17.6%) of the 340 patients in the non-SIC group died. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15-18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23-0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24-55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients. Conclusion SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.

Background Healthcare facility-onset Clostridioides difficile infection is associated with adverse clinical outcomes and hospital reimbursement. A four-year review involving eleven hospitals of the NYC Health + Hospital system was undertaken. Methods From 2016-2019, infection rates and standardized infection ratios (SIRs) were gathered from National Healthcare Safety Network. The C. difficile testing scheme at each facility was recorded. Results For the eleven hospitals, declines in rates of C. difficile infection and SIRs were documented. However, this decline was driven by two hospitals that had high rates of infection in 2016; for the remaining nine hospitals, rates of infection and SIRs were at a plateau. Most hospitals used a testing scheme that fell into the nucleic acid amplification test (NAAT) category for SIR risk adjustment. Hospitals that used the algorithm glutamate dehydrogenase (GDH) and toxin A/B immunoassay (EIA) followed by NAAT for discrepant results had significantly lower rates of C. difficile infection but similar SIRs. Conclusions For most hospitals in this system, rates of C. difficile remained level. Within the NAAT test categories, SIRs may not correlate with infection rates. Given the controversies regarding testing and calculation of SIRs, alternatives to C. difficile infection should be sought as a hospital quality measurement.

In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous with positive surface charges and stable at physiological and acidic pH under certain conditions. They were able to enter into the human keratinocyte cell line (HaCaT), artificial skin membrane (mimicking the human skin), and mouse skin tissue unlike free chondroitin sulfate. The preapplication of nanoparticles also exhibited reduced levels of oxidative stress, cyclobutane pyrimidine dimer formation, TNF-α, and so on in UV-B-irradiated HaCaT cells. In an acute UV-B irradiation mouse model, their topical application resulted in reduced epidermal thickness and sunburn cells, unlike in the case of free chondroitin sulfate. Thus, a completely noninvasive method was used to deliver a bio-macromolecule into the skin without using injections or abrasive procedures.

Background Histiocytic sarcoma is an extremely rare malignant hematological histiocytic neoplasm which is a diagnosis of exclusion based on its morphological and predominantly immunohistochemical criteria. Case description and diagnosis A 63-year female presented with complaints of a midline neck swelling along with right sided neck swelling. On fine-needle aspiration (FNA) from the thyroid lesion and the right cervical lymph node, the smears showed similar findings and a provisional morphological diagnosis of malignant spindle cell neoplasm was kept. On immunohistochemistry, the tumor cells showed immunoreactivity for vimentin, CD45, CD 68 and fascin and were immunonegative for thyroglobulin, S100, CD21, CD3, CD4 and other markers. Based on the immunohistochemical profile, a diagnosis of histiocytic sarcoma was established. Conclusion Histiocytic sarcoma is a rare malignant neoplasm that can be easily missed in thyroid resembling an anaplastic carcinoma.

Purpose The aim of this study was to compare the efficacy and safety of standard [Ultraviolet (UV) light power: 3 mW/cm2, duration: 30 minutes] versus accelerated (UV power: 9 mW/cm2, duration: 10 minutes) corneal crosslinking (CXL) for stabilizing keratoconus. Methods A total of 684 eyes (555 patients; mean age ± SD, 25.0 ± 7.9 years; women, 30.6%) from 24 international sites with epithelium-off CXL for keratoconus had follow-up data at 1-year and met the inclusion criteria. Two hundred sixty-six eyes (228 patients) had undergone standard CXL, and 418 eyes (327 patients) had undergone accelerated CXL. The outcome measures included changes in visual acuity, keratometry, minimum corneal thickness, and frequency of adverse events. The outcomes were compared using mixed-effects regression models adjusted for age, sex, visual acuity, keratometry, pachymetry, doctor, practice, and eye laterality. Results The adjusted mean changes (95% confidence interval) in outcomes were similar in standard and accelerated CXL in visual acuity [6.5 (2.0, 11.1) versus 5.5 (0.4, 10.6) logMAR letters, respectively], Kmax [-0.9 (-1.4, -0.3) D versus -1.2 (-1.9, -0.4) D, respectively], K2 [-0.4 (-0.9, 0.2) D versus -0.4 (-1.1, 0.3), D respectively], or minimum corneal thickness [-13.3 (-20.3, -6.3) μm versus -16.6 (-24.5, -8.6) μm, respectively] (all P > 0.05). The frequency of adverse events at the 12-month visit was also similar between the CXL groups (standard, 8.3% vs. accelerated, 5.5%; P = 0.21). Conclusions This real-world observational study found that both standard and accelerated CXL were similarly safe and effective in stabilizing keratoconus at 1-year postsurgery in the real-world setting. The findings support the adoption of accelerated CXL for time and convenience.

The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the efficacy of such treatments has been observed in both preclinical studies and clinical trials, there are issues pertaining to the use of these drugs which require more extensive research with regards to the delivery and stability of siRNAs and ASOs. This would improve their use for long-term treatment regimens and alleviate the difficulties experienced by patients with ocular diseases. This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-LRX in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology.

Phototherapeutic keratectomy (PTK) with 193-nm excimer laser is a safe and effective procedure for the treatment of superficial corneal pathology. We aimed to review the use of PTK for the treatment of corneal macular dystrophy (MCD).Case report and literature review.A 16-year-old boy presented to an ophthalmologist with a 4-year history of reduced vision, glare and photophobia in his left eye. He was diagnosed with corneal macular dystrophy and underwent sequencing of the CHST6 gene. Left excimer PTK with mitomycin C was performed. He remained relapse free until 18 months post procedure when his visual acuity declined and the stroma appeared more "milky". He underwent a penetrating keratoplasty in his left eye 24 month following the initial PTK.Phototherapeutic keratectomy is an effective means of visual restoration in patients with macular corneal dystrophy and may delay penetrating keratoplasty. Patients should be counselled regarding the high risk of recurrence. This is the first reported case of a CHST6 gene positive patient with MCD that was treated with phototherapeutic keratoplasty.

SGLT-2 inhibitors are known to increase hematocrit. We present two cases with marked asymptomatic erythrocytosis developing after taking SGLT-2 inhibitors. No other predisposing or causative factor was found and SGLT-2 inhibitor drug was the most likely cause in both cases. Both patients underwent phlebotomy and haematocrit came down after withdrawing the offending drug.

Background: India is considered the world capital of diabetes, proper care and management of the same is the demand of society. The present study is carried out to identify the disease burden of GDM/ overt DM among antenatal cases. The main objective was to study the maternal and fetal outcome of diabetes complicating pregnancy.Methods: The present study was conducted at Dr. Rajendra Prasad Government Medical College at Tanda, District KangraHP from October 2015 to September 2016. All antenatal cases were screened for diabetes by OGTT 75 gm, 2-hour blood glucose level as per DIPSI guidelines and labelled as GDM/ overt DM. Those who fulfilled selection criteria were enrolled in the study. A total of 6452 cases who attended antenatal clinic during the study duration and were screened were selected for the study. 116 cases were found to have GDM / overt DM. Seventy-nine had GDM with OGTT>140 mg/dl (DIPSI guidelines) and 37 had overt DM with 2 hours PP >200 mg/dl (WHO criteria). Total 100 cases comprised of study group were followed till delivery to study maternal and fetal outcome.Results: The prevalence of diabetes in pregnancy was found to be low 1.79%. GDM was found to be more prevalent than overt diabetes in pregnant women (66% versus 34%). Among the antenatal maternal complications observed missed abortion (11.8% versus 1.55; p=0.026), polyhydraminos (26.4% versus 10.6%; p=0.04) and preterm labour (17.6% versus 4.5%; p=0.003) were significantly more common in overt diabetics than GDM cases. IUFD (8.8% versus 0; p=0.014) was also significantly more common in overt diabetics than GDM case. RDS was found significantly higher in neonates of overt diabetics as compared to GDM mothers (14.7 % versus 1.5%; p=0.009).Conclusions: Early detection and good glycemia control by MNT and insulin, regular antenatal check-ups, patient counselling and compliance, intrapartum fetal monitoring and early neonatal care are keys to improved outcome.

This article investigates the dynamics of relationship between foreign direct investment (FDI) inflows and major macroeconomic variables, i.e. gross domestic product (GDP), exports and exchange rat...

DivIVA or Wag31, which is an essential pole organizing protein in mycobacteria, can self-assemble at the negatively curved side of the membrane at the growing pole to form a higher order structural scaffold for maintaining cellular morphology and localizing various target proteins for cell-wall biogenesis. The structural organization of polar scaffold formed by polymerization of coiled-coil rich Wag31, which is implicated in the anti-tubercular activities of amino-pyrimidine sulfonamides, remains to be determined. A single-site phosphorylation in Wag31 regulates peptidoglycan biosynthesis in mycobacteria. We report biophysical characterizations of filaments formed by mycobacterial Wag31 using circular dichroism, atomic force microscopy and small angle solution X-ray scattering. Atomic force microscopic images of the wild-type, a phospho-mimetic (T73E) and a phospho-ablative (T73A) form of Wag31 show mostly linear filament formation with occasional curving, kinking and apparent branching. Solution X-ray scattering data indicates that the phospho-mimetic forms of the Wag31 polymers are on average more compact than their phospho-ablative counterparts, which is likely due to the extent of bending/branching. Observed structural features in this first view of Wag31 filaments suggest a basis for higher order Wag31 scaffold formation at the pole.

How proteins localize at the pole remains an enigma. DivIVA/Wag31, which is an essential pole organizing protein in mycobacteria, can assemble at the negatively curved side of the membrane at the growing pole to form a higher order structural scaffold for maintaining cellular morphology and localizing various target proteins for cell-wall biogenesis. A single-site phosphorylation in Wag31 is linked to the regulation of peptidoglycan biosynthesis for optimal mycobacterial growth. The structural organization of polar scaffold formed by coiled-coil rich Wag31, which is a target for anti-tubercular agent amino-pyrimidine sulfonamide, remains to be determined. Here, we report biophysical characterizations of a phospho-mimetic (T73E) and a phospho-ablative (T73A) form of mycobacterial Wag31 using circular dichroism, small angle solution X-ray scattering and atomic force microscopy. While data obtained from both variants of Wag31 in solution states suggested formation of alpha-helical, large, elongated particles, their structural organizations were different. Atomic force microscopic images of Wag31 indicate polymer formation, with occasional curving, sharp bending and branching. Observed structural features in this first view of the polymeric forms of Wag31 suggest a basis for higher order network scaffold formation for polar protein localization.

Physician impairment is a critical issue in health care setting. Physicians have an exaggerated risk of psychosocial problems. The most common psychiatric problems in the physician can be isolated psychiatric conditions or substance abuse. Physician impairment due to psychosocial problems, substance abuse, burnout or accidental health care hazards can result in adverse personal, social and professional consequences. Due to the nature of the work, physician impairment can result in significant compromise in patients’ health. It is absolute necessary to have a definitive set of programs within each health care facility to target physician impairment preserving the functionality and optimal health output of health care provider and the receiver.