Comparison of Patient Satisfaction between Invisible Appliance and Fixed Orthodontic Appliances - A Systematic Review.

To compare the patient acceptance between fixed orthodontic appliances and clear aligners. An electronic search was completed in PubMed, Cochrane Database, Web of Science, Scopus, Lilacs, Google Scholar, and Open Grey databases without any restrictions until August 23. All comparative study types contrasting patient perception between clear aligners and fixed appliances were included. After removal of duplicates, exclusion by title and abstract, and reading the full text, only eight articles were included. The studies used an observational questionnaire study design. Of the observational studies, one was retrospective and three prospective, one online survey, and the other three cross sectional. Though the response varied in terms of patient preference and acceptance, it was found that clear aligners have a positive impact with respect to quality of life, tolerance, and improved confidence. However, there is not enough evidence to make a final conclusion about treatment outcomes.

Conservative Management of a Case of Peripartum Cardiomyopathy in a Young Multigravida.

Peripartum cardiomyopathy (PPCM) is a rare disorder that generally affects the elderly multigravida females. It is a type of dilated cardiomyopathy that generally affects the last trimester of pregnancy or early postpartum period. Several risk factors are associated with the development of PPCM. Even though PPCM has greater morbidity, if managed promptly, it can be reverted with minimal morbidity or mortality. We present a case of a young woman, multigravida, with moderate anemia corrected, who was taken for emergency lower segment cesarean section, without previous cardiac evaluation, and ended up with pulmonary edema intraoperatively. Later on, her evaluation was done which came out to be PPCM. She was managed conservatively thereafter with no significant morbidity and a good maternal and perinatal outcome. We should be alert in diagnosing a case of PPCM with prompt treatment to reduce mortality. Cardiovascular conditions cause approximately 26 percent of pregnancy-related deaths which include valvular heart disease and congenital heart disease. Appropriate diagnosis and management are necessary for preventing mishaps.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

A NANOG-pERK reciprocal regulatory circuit regulates Nanog autoregulation and ERK signaling dynamics.

The self-renewal and differentiation potential of embryonic stem cells (ESCs) is maintained by the regulated expression of core pluripotency factors. Expression levels of the core pluripotency factor Nanog are tightly regulated by a negative feedback autorepression loop. However, it remains unclear how ESCs perceive NANOG levels and execute autorepression. Here, we show that a dose-dependent induction of Fgfbp1 and Fgfr2 by NANOG activates autocrine-mediated ERK signaling in Nanog-high cells to trigger autorepression. pERK recruits NONO to the Nanog locus to repress transcription by preventing POL2 loading. This Nanog autorepression process establishes a self-perpetuating reciprocal NANOG-pERK regulatory circuit. We further demonstrate that this reciprocal regulatory circuit induces pERK heterogeneity and ERK signaling dynamics in pluripotent stem cells. Collectively our data suggest that NANOG induces Fgfr2 and Fgfbp1 to activate ERK signaling in Nanog-high cells to establish a NANOG-pERK reciprocal regulatory circuit. This circuit regulates ERK signaling dynamics and Nanog autoregulation in pluripotent cells.

How Should Surgical Palliative Success Be Defined?

Palliative surgery is often defined as surgical intervention with intent to improve a patient's quality of life by relieving suffering secondary to symptoms of advanced disease. In the context of shared decision making about palliative surgery intervention, tensions can arise between patient (or surrogate) and surgeon, who might not share goals and values. This article suggests that a surgeon's clinical and ethical duty is to identify goals of care, including those related to quality of life, from a patient's perspective and to consider how to achieve them.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

Sentinel Contributions of US Department of Veterans Affairs Surgeons in Shaping the Face of Health Care.

The vast accomplishments of the US Department of Veterans Affairs (VA) during the past century have contributed to the advancement of medicine and benefited patients worldwide. This article highlights some of those accomplishments and the advantages in the VA system that promulgated those successes. Through its affiliation with medical schools, its formation of a structured research and development program, its Cooperative Studies Program, and its National Surgical Quality Improvement Program, the VA has led the world in the progress of health care. The exigencies of war led not only to the organization of VA health care but also to groundbreaking, landmark developments in colon surgery; surgical treatments for vascular disease, including vascular grafts, carotid surgery, and arteriovenous dialysis fistulas; cardiac surgery, including implantable cardiac pacemaker and coronary artery bypass surgery; and the surgical management of many conditions, such as hernias. The birth of successful liver transplantation was also seen within the VA, and countless other achievements have benefited patients around the globe. These successes have created an environment where residents and medical students are able to obtain superb education and postgraduate training and where faculty are able to develop their clinical and academic careers.

Anti-retroviral therapy failure in HIV-1 infected pregnant women and its associated risk of HIV transmission.

BACKGROUND: The HIV perinatal transmission in India even after interventions is still high. The anti-retroviral therapy failure rate and the risk of HIV vertical transmission to infants from women with failed treatment during pregnancy also largely remains unevaluated. METHODS: This is a prospective, observational and follow-up study of 18 months to determine the association of ART failure in pregnant women and the subsequent risk of HIV transmission to their infants. A total of 81 mothers were evaluated for ART success/failure by analysing their viral loads. RESULTS: Analyses revealed that a high percentage (19.75%) of women on ART had high viral loads, while the overall HIV transmission rate to the infants was 8.64%. The rate of transmission from women with high viral load was significantly high compared to women with low viral load (37.5% vs. 1.54%; p = 0.0015). CD4 level was not associated with HIV transmission. However, CD4 levels in women, who had successful or failed ART, were significantly different (p = 0.0031). Factors such as mother's age, baby's sex and weight as well as delivery mode were not associated with HIV transmission, however, breastfeeding and viral loads were found to be independently associated with HIV transmission to the neonates. CONCLUSIONS: This study highlights that a significant proportion of women on ART had impaired viral load control. The rate of HIV transmission to infants was also significantly high among these women. This warrants viral load monitoring of HIV infected women to reduce the overall transmission to the infants.

Visualizing the translation and packaging of HIV-1 full-length RNA.

HIV-1 full-length RNA (HIV-1 RNA) plays a central role in viral replication, serving as a template for Gag/Gag-Pol translation and as a genome for the progeny virion. To gain a better understanding of the regulatory mechanisms of HIV-1 replication, we adapted a recently described system to visualize and track translation from individual HIV-1 RNA molecules in living cells. We found that, on average, half of the cytoplasmic HIV-1 RNAs are being actively translated at a given time. Furthermore, translating and nontranslating RNAs are well mixed in the cytoplasm; thus, Gag biogenesis occurs throughout the cytoplasm without being constrained to particular subcellular locations. Gag is an RNA binding protein that selects and packages HIV-1 RNA during virus assembly. A long-standing question in HIV-1 gene expression is whether Gag modulates HIV-1 RNA translation. We observed that despite its RNA-binding ability, Gag expression does not alter the proportion of translating HIV-1 RNA. Using single-molecule tracking, we found that both translating and nontranslating RNAs exhibit dynamic cytoplasmic movement and can reach the plasma membrane, the major HIV-1 assembly site. However, Gag selectively packages nontranslating RNA into the assembly complex. These studies illustrate that although HIV-1 RNA serves two functions, as a translation template and as a viral genome, individual RNA molecules carry out only one function at a time. These studies shed light on previously unknown aspects of HIV-1 gene expression and regulation.

Seroprevalence of Toxoplasma gondii in newly diagnosed HIV seropositive patients.

BACKGROUND & OBJECTIVES: Immunocompromised individuals mainly HIV infected patients are at a great risk for developing toxoplasmosis. The presence of toxoplasmosis among HIV-infected patients directly correlates with the prevalence of anti- Toxoplasma gondii antibodies and the degree of immunosuppression (measured by CD4 counts). The data regarding the seroprevalence of toxoplasmosis in HIV-infected patients are scarce in India. Therefore, this study was initiated to find out the seroprevalence of toxoplasmosis in treatment-naïve HIV seropositive patients and to determine its association with CD4 counts, if any. METHODS: Four hundred newly diagnosed antiretroviral therapy (ART) naïve adult HIV positive patients coming for CD4 count estimation were tested for the presence of anti- Toxoplasma IgG antibodies. Risk factors for acquisition of toxoplasmosis as well as the age, gender and CD4 counts of the patient were noted down. RESULTS: Toxoplasma IgG was positive in 292 (73%) patients, and the positivity was not related to their CD4 counts. The proportion of anti- Toxoplasma IgG positivity showed no significant association with age, gender and risk factors of the patients. INTERPRETATION & CONCLUSIONS: In the absence of any specific vaccine or prophylaxis for toxoplasmosis, it is pertinent to screen all HIV-positive patients for Toxoplasma IgG at diagnosis, irrespective of their CD4 counts, and sensitize them about the means to prevent either acquisition or activation of infection to avert the development of toxoplasmic encephalitis.

Distribution of human leucocyte antigen-C in HIV-1-infected patients in Mumbai, India.

HIV pathogenesis is known to be highly influenced by host genetic factors, such as human leucocyte antigens (HLAs) HLA-A and HLA-B. However, the role of HLA-C remains largely unexplored. We evaluated HLA-C distribution in 186 HIV-1-infected individuals and compared them to ethnically matched data derived from the Allele Frequency Net Database using Chi-square test with Fisher's exact two-tailed test. The frequency of HLA-C*05 and HLA-C*15 was higher in infected group, whereas the frequency of HLA-C*04 and HLA-C*14 was higher in control group. HLA-C*17, a rare allele, was significantly higher in infected group. These data could be useful in designing and testing vaccines in Indian population.

Perianal Basal Cell Carcinoma Successfully Managed with Excisional Biopsy.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy in the United States and is often nonaggressive. Its location in the perianal region is very rare and it is estimated that only 0.08% of all BCCs occur in this region. Herein, we present a case of perianal basal cell carcinoma, nodular type. The diagnosis was made using excisional biopsy of a skin lesion. Immunohistochemical staining confirmed the diagnosis: it showed diffuse and strong positivity for smooth muscle actin (SMA) and monoclonal antibody BER-Ep4 and was negative for carcinoembryonic antigen (CEA), pancytokeratin (AE1/AE3), and epithelial membrane antigen (EMA). The treatment of choice has traditionally been local excision to clear margins but the newest guidelines recommend Mohs Micrographic surgery (MMS) or standard 4mm surgical margins for this high-risk BCC. Our patient was successfully treated using excisional biopsy without recurrence. In select patients with lesions smaller than 1cm, excisional biopsy may be sufficient to treat the disease and may be better tolerated than MMS and wider surgical margins. Literature review suggests a predisposition for perianal BCC in individuals susceptible to cutaneous malignancies. Therefore, any history of cutaneous malignancy should further prompt clinicians to examine nonsun exposed areas on full body skin exams.

Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India.

RATIONALE: Vancomycin remains the standard of care for gram-positive bacterial infections, though there are significant developments in newer antibacterial agents. Efficacy can be improved by linking pharmacokinetic with pharmacodynamic principles, thus leading to optimum antibiotic exposure. There is scarcity of pharmacokinetic data in Indian intensive care unit (ICU) population. MATERIALS AND METHODS: Fifteen subjects with suspected or proven gram-positive bacterial infection of either gender between 18 years and 65 years of age were enrolled. Vancomycin at the dose of 1 g every 12 hours was administered over 1-hour period and pharmacokinetic assessments performed on blood samples collected on days 1 and 3. Vancomycin concentrations were measured on validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO). RESULTS: The mean C max, elimination half-life, AUC0-12hours, volume of distribution, and clearance of single dose were 36.46 µg/mL (±14.87), 3.98 hours (±1.31), 113.51 µg/mL (±49.51), 52.01 L (±31.31), and 8.90 mL/minute (±3.29), respectively, and at steady state were 40.87 µg/mL (±19.29), 6.27 hours (±3.39), 147.94 µg/mL (±72.89), 56.39 L (±42.13), and 6.98 mL/minute (±4.48), respectively. The elimination half-life increased almost two-fold at steady state. The steady state mean AUC0-24 was 295.89 µg/mL (±153.82). Out of 45 trough levels, 32 (71.11%) concentrations were below recommended range. CONCLUSION: Recommended AUC0-24hours and trough concentrations were not achieved in majority of patients with current dosing, suggesting reevaluation of current vancomycin dosing. Individualized treatment based on close monitoring of vancomycin serum concentrations in critically ill patients is imperative. HOW TO CITE THIS ARTICLE: Mali NB, Deshpande SP, Wandalkar PP, Gupta VA, Karnik ND, Gogtay NJ, et al. Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India. IJCCM 2019;23(11):513-517.

Benefit of N-Acetylcysteine in Postoperative Hepatic Dysfunction: Case Report and Review of Literature.

N-Acetylcysteine (NAC) is reported to have multiple clinical applications in addition to being the specific antidote for acetaminophen toxicity. NAC stimulates glutathione biosynthesis, promotes detoxification, and acts directly as a scavenger of free radicals. It is a powerful antioxidant and a potential treatment option for diseases characterized by the generation of free oxygen radicals. We present a case of postoperative hepatic dysfunction of multifactorial etiology in a patient with therapeutic acetaminophen levels, where hepatic function improved considerably following administration of intravenous NAC. This case suggests that NAC should be considered for treatment of acute liver dysfunction in the postoperative setting, even in the absence of elevated acetaminophen levels.