Identifying Populations at Risk for Lung Cancer Mortality from the National Health and Nutrition Examination Survey (2001-2018) Using the 2021 USPSTF Screening Guidelines.

Lung cancer (LC) is the leading cause of cancer mortality in the United States. To combat this predicament, early screening and critically assessing its risk factors remain crucial. The aim of this study was to identify the value of specific factors from the National Health and Nutrition Examination Survey (NHANES) from 2001-2018, as they relate to lung cancer mortality in the US Preventive Services Task Force (USPSTF)-eligible population. A total of 3545 adults who met USPSTF criteria were extracted from 81,595 NHANES participants. The LC Death Risk Assessment Tool was used to calculate the number of deaths per 1000 individuals. The Mann-Whitney U test and one-way ANOVA determined the statistical significance of the factors involved in LC mortality. Male sex, African and Hispanic ethnicity, lower education attainment, and secondhand exposure to cigarette smoke correlated with an increased risk of LC mortality. Additionally, the factor of emotional support from NHANES data was analyzed and did not show any benefit to reducing risk. By identifying individuals at high-risk, preventative measures can be maximized to produce the best possible outcome.

Gestational Diabetes Mellitus in a Multi-Ethnic, High-Risk Population: Adequacy of Screening for Diabetes Mellitus 6 Weeks after Delivery.

Gestational diabetes mellitus (GDM) during pregnancy is a marker for future type 2 diabetes mellitus (T2DM); therefore, a meticulous follow-up after delivery can help identify women at risk for T2DM. In a cohort of 5504 pregnant women, the postpartum follow-up of all 1043 women with GDM for hyperglycemia in a multi-ethnic, high-risk Arab population was investigated. The prevalence of GDM was 18.9%. A total of 265 (25.4%) women returned for an oral glucose tolerance test (OGTT) 4-6 weeks after delivery, with more South Asian than Arab women (p < 0.01). The other factors associated with return were (a) family history of T2DM, (b) lower basic metabolic index, (c) higher abortions and (d) lower gravida (p < 0.05), all with minimal effect. An abnormal postpartum OGTT was statistically associated with previous GDM history and hypoglycemic drug treatment, although these effects were small. Overall, the follow-up of women with GDM postpartum was dismal, ethnicity being the major factor influencing return. Urgent public measures are needed to educate women with GDM about follow-up highlighting (a) risk awareness for T2DM and (b) a healthy lifestyle after childbirth-if we are to turn the tide on the epidemic of T2DM plaguing the Arab world.

Altruism as an Explanation for Human Consanguinity.

BACKGROUND: Human inbreeding is a sociobiological puzzle. Despite widespread knowledge of its potential for genetic disorders, human consanguinity remains surprisingly common. The current reasons explaining its continued persistence in today's modern world have major shortcomings. SUMMARY: We propose that the Neolithic Agrarian revolution modified the structure of populations. It increased competition for the limited resources in which a larger group had better chances of survival. As a result, small, drifting, socially open bands of hunter-gatherers were transformed into bigger, less mobile, and more powerful kinship groups (tribes). In this transformation, a central role was played by human trust - an aspect of human altruism which is a universal sociobiological principle of behavior. Altruism (and trust) is an essential premise of social contracts such as economic cooperation, marriage arrangement, and creation of alliances between people. In kinship groups, human trust is limited to kin, so tribes remain small, economically poor, and consanguineous due to lack of nonkin mates. The expanding of trust from kin to that of nonbiological relatives increases the size of human groups, fosters economic wealth, and decreases the rate of consanguinity. Key Messages: The lack of nonkin altruism leads to: (a) poverty (due to poor economic cooperation with nonkin), (b) maintaining small group size, and (c) inbreeding.

Negotiating Gestational Diabetes Mellitus in India: A National Approach.

The worldwide epidemic of diabetes mellitus and hyperglycemia in pregnancy (HIP) presents many challenges, some of which are country-specific. To address these specific problems, parochial resolutions are essential. In India, the government, by working in tandem with (a) national groups such as the Diabetes in Pregnancy Study Group of India, and (b) global organizations such as the International Diabetes Federation, has empowered the medical and paramedical staff throughout the country to manage HIP. Additionally, despite their academic university backgrounds, Indian health planners have provided practical guidelines for caregivers at the ground level, who look up to these experts for guidance. This multipronged process has helped to negotiate some of the multiple problems that are indigenous and exclusive to India. This review traces the Indian journey to manage and prevent HIP with simple, constructive, and pragmatic solutions.

Gestational Diabetes in the Arab Gulf Countries: Sitting on a Land-Mine.

Type 2 diabetes mellitus (T2DM) has become a modern-day plague by reaching epidemic levels throughout the world. Due to its similar pathogenesis, gestational diabetes (GDM) increases in parallel to T2DM. The prevalence of T2DM (3.9-18.3%) and GDM (5.1-37.7%) in countries of the Arab Gulf are amongst the highest internationally, and they are still rising precipitously. This review traces the reasons among the Arab nations for (a) the surge of T2DM and GDM and (b) the failure to contain it. During the last five decades, the massive oil wealth in many Arab countries has led to the unhealthy lifestyle changes in physical activity and diet. The excess consumption of calories turned the advantageous genes, originally selected for the famine-like conditions, detrimental: fueling obesity and insulin resistance. Despite genetic differences in these populations, GDM-a marker for future obesity and T2DM-can overcome this scourge of T2DM through active follow-up and screening after delivery. However, the health policies of most Arab countries have fallen short. Neglecting this unique chance will miss an irreplaceable opportunity to turn the tide of the T2DM and obesity epidemic in the Middle Eastern Arab Gulf countries-as well as globally.

A Prospective Multicentric Postmarketing Observational Study to Characterize the Patient Population with Reduced Gastrointestinal Motility among Indian Diabetic Patients Receiving Itopride: The Progress Study.

AIMS: This study was intended to assess the clinical profile of Indian diabetic patients with reduced gastrointestinal (GI) motility and to understand the role of itopride in addressing reduced GI motility (gastroparesis) symptoms and maintaining glycemic control. MATERIAL AND METHODS: Patients with established reduced GI motility (scintigraphy), with varying degree of GI symptoms, receiving itopride 150 mg as per physicians' discretion were enrolled. Clinical profile, changes in symptom severity, glycemic indices, tolerability, and quality of life (QoL) after 8-week therapy (Patient assessment of upper GI disorders-QoL [PAGI-QoL]) were assessed. RESULTS: Mean ± standard deviation age of enrolled population (n = 41) was 51.8 ± 12.39 years. Average duration of gastroparesis since underlying etiology was 67.7 ± 59.76 months. Common symptoms reported at baseline were bloating (68.3%), postprandial fullness (61.0%), nausea (51.2%), early satiety (41.5%), heartburn (39.0%), and vomiting (9.8%). Itopride therapy resulted in significant improvement in all symptoms (P < 0.001), which correlated with improved QoL (PAGI-QoL score reduction: 13.8 ± 11.48; P < 0.0001). Moreover, significant improvement in glycemic indicators was also evident (mean change from baseline hemoglobinA1c -0.5 ± 1.18; fasting plasma glucose -15.3 ± 43.61; postprandial plasma glucose -24.6 ± 57.20). CONCLUSIONS: Itopride showed effectiveness in addressing symptoms of reduced GI motility in diabetics, with improved QoL. Significant improvement in glycemic indices was also evident posttreatment with itopride. This study sheds light on the role of prokinetics, not only for symptom relief but also for improving glycemic control in diabetic patients with reduced GI motility, thus providing a holistic approach for the management of these patients.

A Phase III open-label, randomized, active controlled clinical study to assess safety, immunogenicity and lot-to-lot consistency of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants.

BACKGROUND: A heat-stable bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was developed in India. In this study, the vaccine was tested for safety, immunogenicity and clinical lot-to-lot consistency. METHODS: This was a Phase III, open label, randomized, equivalence design study. The primary objective was to demonstrate lot-to-lot consistency of BRV-PV. Subjects were randomized into four arms, three arms received Lots A, B, and C of BRV-PV and the control arm, received Rotarix®. Three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. The three lots of BRV-PV were equivalent if the 95% Confidence Intervals (CIs) of the geometric mean concentration (GMC) ratios were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: The study was conducted in 1500 randomized infants, of which 1341 infants completed the study. The IgA GMC ratios among the three lots were around 1 (Lot A versus Lot B: 1.07; Lot A versus Lot C: 1.06; and Lot B versus Lot C: 0.99). The 95% CIs for the GMC ratios were between 0.78 and 1.36. The IgA GMCs were: BRV-PV group 19.16 (95% CI 17.37-21.14) and Rotarix® group 10.92 (95% CI 9.36-12.74) (GMC ratio 1.75; 90% CI 1.51-2.04). Seropositivity rates were 46.98% (95% CI 43.86-50.11) and 31.12% (95% CI 26.17-36.41). The incidence of solicited reactions was comparable across the four arms. No serious adverse events were associated with the study vaccines, except two gastroenteritis events in the BRV-PV groups. CONCLUSION: Lot-to-lot consistency of BRV-PV was demonstrated in terms of GMC ratios of IgA antibodies. The vaccine safety and immunogenicity profiles were similar to those of Rotarix®. Clinical Trials.Gov [NCT02584816] and Clinical Trial Registry of India [CTRI/2015/07/006034].

Macromolecular crowding-induced molten globule states of the alkali pH-denatured proteins.

Structural and molecular properties extracted from circular dichroism (CD), tryptophan fluorescence and 1-anilino-8-napthalene sulfonate (ANS) binding experiments suggest that the high concentration of synthetic crowding agents (dextran 40, dextran 70 and ficoll 70) stabilizes and refolds the base-denatured ferricytochrome c (Ferricyt c) and lysozyme (Lyz) at pH 12.9 (±0.1) to molten globule (MG) states (CB-states). These results further revealed that the CB-states resemble the generic properties of MG-states. Thermodynamic analysis of thermal denaturation curves of base-denatured Ferricyt c and Lyz at pH 12.9 (±0.1) under variable concentrations of crowding agents (dextran 40, dextran 70 and ficoll 70) revealed that the crowder presence increases the thermal stability of base-denatured proteins and also prevents the cold denaturation of Ferricyt c. The results further showed that the nature, size and shape of crowder influence the crowding-mediated increase in secondary structure stabilization and thermal stability of base-denatured Ferricyt c and Lyz. Analysis of kinetic and thermodynamic parameters measured for CO association reaction of alkaline ferrocytochrome c (Ferrocyt c) at pH 12.9 (±0.1) under variable concentrations of crowding agents (dextran 40, dextran 70 and ficoll 70) revealed that the crowder presence reduces the level of structural fluctuation of M80-containing Ω-loop that control CO association to alkaline Ferrocyt c.

A survey of retaining faculty at a new medical school: opportunities, challenges and solutions.

BACKGROUND: At well-established academic university settings, retaining faculty remains a pressing challenge due to competing market forces, decreasing institutional support, and changing personal expectations. There is a paucity of information about the difficulties faced by new medical schools to maintain their academic workforce. The objective of this study was to determine the challenges facing the faculty at a newly developed medical school. METHODS: Twelve founding faculty were surveyed anonymously by a 32-item questionnaire. Their responses were independently analyzed by three researchers. RESULTS: The views of the faculty were categorized into in four inter-related themes: personal, support, institutional, and environmental. The constant sources of satisfaction among faculty were higher academic rank (75%), harmonious inter-collegial relationships (74%), healthy pecuniary rewards (58%), better professional growth (58%) along with greater autonomy, administrative independence, minimum groupism and excellent team work. Poor opportunities for promotion (68%), reduced support for scholarly activities (67%) and unsatisfactory support from the administration (55%) were detrimental to retaining faculty. CONCLUSION: By addressing specific issues facing its staff, every new medical school will not only manage to retain its academic faculty but also be able to attract well qualified academic staff from established medical institutions worldwide.

Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine.

BACKGROUND: A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. METHODS: In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. RESULTS: A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. CONCLUSION: BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Curriculum mapping as a tool to facilitate curriculum development: a new School of Medicine experience.

BACKGROUND: Every curriculum needs to be reviewed, implemented and evaluated; it must also comply with the regulatory standards. This report demonstrates the value of curriculum mapping (CM), which shows the spatial relationships of a curriculum, in developing and managing an integrated medical curriculum. METHODS: A new medical school developed a clinical presentation driven integrated curriculum that incorporates the active-learning pedagogical practices of many educational institutions worldwide while adhering to the mandated requirements of the accreditation bodies. A centralized CM process was run in parallel as the curriculum was being developed. A searchable database, created after the CM data was uploaded into an electronic curriculum management system, was used to ensure placing, integrating, evaluating and revising the curricular content appropriately. RESULTS: CM facilitated in a) appraising the content integration, b) identifying gaps and redundancies, c) linking learning outcomes across all educational levels (i.e. session to course to program), c) organizing the teaching schedules, instruction methods, and assessment tools and d) documenting compliance with accreditation standards. CONCLUSIONS: CM is an essential tool to develop, review, improve and refine any integrated curriculum however complex. Our experience, with appropriate modifications, should help other medical schools efficiently manage their curricula and fulfill the accreditation requirements at the same time.

Effects of lyotropic anions on thermodynamic stability and dynamics of horse cytochrome c.

This paper evaluates the effect of various lyotropic anions (chloride, sulfate, perchlorate, iodide, nitrate, bromide) on the thermodynamic stability and dynamics of native cytochrome c (Cyt c) at pH 7.0. The results of equilibrium and kinetic studies revealed that: (i) at low to intermediate concentrations (≤ 0.5 M), both chaotropic and kosmotropic anions restrict the dynamics of native protein, (ii) at relatively higher concentrations (≥ 1.0 M), the denaturing effect of chaotropic anions dominates, which increases the level of structural-fluctuations responsible to unfold the protein according to Hofmeister series (perchlorate > iodide > nitrate > bromide), and (iii) the lyotropic anions affect the thermal and global stability of Cyt c according to Hofmeister series. The m-value was determined from ΔΔG vs [Cosolute] plot and was found to be positive for sulfate and negative for other anions consistent with effect of lyotopic anions on protein stability according to Hofmeister series.

Consensus in Gestational Diabetes MELLITUS: Looking for the Holy Grail.

The world's pre-eminent diabetes, obstetric, endocrine, and health organizations advocate a plethora of diverse algorithms for the screening, diagnosis, management, and follow-up of gestational diabetes mellitus (GDM). Additionally, there are regional recommendations of local health societies. Several of these proposals for GDM are contentious because some of them were developed from unscientific studies, based on expert-opinion, catered to preserve resources, and subjectively modified for convenience. Due to the wide variety of choices available, the approach to GDM can be extremely diverse even within the same hospital. This lack of consensus creates major problems in addressing prevalence, complications, efficacy of treatment, and follow-up of GDM. Moreover, it becomes nearly impossible to compare the numerous studies. Furthermore, the lack of consensus confuses the health care providers of obstetric health who look to the experts for guidance. Therefore, a clear, objective, "evidence-based" global approach, which is simple, easy to follow, and validated by corroborative research, is crucial. We contend that, despite decades of research, a single acceptable global guideline is not yet on the horizon.

Gestational Diabetes Mellitus: Using the Fasting Plasma Glucose Level to Simplify the International Association of Diabetes and Pregnancy Study Groups Diagnostic Algorithm in an Adult South Asian Population.

OBJECTIVES: To evaluate the value of the fasting plasma glucose (FPG) level for simplifying the International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic algorithm of gestational diabetes mellitus (GDM) in a South Asian population. METHODS: In 6,520 pregnant women undergoing universal screening with the 75 g oral glucose tolerance test (OGTT), the area under receiver operating characteristic curve was used to determine the overall FPG performance to detect GDM (IADPSG criteria). Specifically, 2 different FPG thresholds of the OGTT were used to rule in and rule out GDM so as to decrease the need for the cumbersome OGTT. RESULTS: GDM was present in 1,193 (18.3%) women. The FPG 1) area under receiver operating characteristic curve (95% CI) was 0.909 (0.898 to 0.920); 2) threshold of ≥5.1 mmol/L independently could rule in GDM in 708 (10.9%) women (100% specificity); 3) threshold of <4.3 mmol/L independently could rule out GDM in an additional 2,389 (36.6%) women (95.6% sensitivity). CONCLUSIONS: By circumventing nearly one half the OGTTs, an initial FPG can simplify the onerous GDM diagnostic IADPSG algorithm in this population parochially and in countries with large South Asian immigrant populations-without compromising medical care.

Breast cancer protection by genomic imprinting in close kin families.

Human inbreeding generally reduces breast cancer risk (BCR). When the parents are biologically related, their infants have a lower birth weight due to smaller body organs. The undersized breasts, because of fewer mammary stem cells, have a lower likelihood of malignant conversion. Fetal growth is regulated by genomically imprinted genes which are in conflict; they promote growth when derived from the father and suppress growth when derived from the mother. The kinship theory explicates that the intensity of conflict between these genes affects growth and therefore the size of the newborn. In descendants of closely related parents, this gene clash is less resulting in a smaller infant. In this review, we elucidate the different mechanisms by which human inbreeding affects BCR, and why this risk is dissimilar in different inbred populations.

Gestational diabetes mellitus: Screening with fasting plasma glucose.

Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman.

Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53.

Inactivation of the p53 tumor suppressor by mutation or overexpression of negative regulators occurs frequently in cancer. As p53 plays a key role in regulating proliferation or apoptosis in response to DNA-damaging chemotherapies, strategies aimed at reactivating p53 are increasingly being sought. Strategies to reactivate wild-type p53 include the use of small molecules capable of releasing wild-type p53 from key, cellular negative regulators, such as Hdm2 and HdmX. Derivatives of the Hdm2 antagonist Nutlin-3 are in clinical trials. However, Nutlin-3 specifically disrupts Hdm2-p53, leaving tumors harboring high levels of HdmX resistant to Nutlin-3 treatment. Here, we identify CTX1, a novel small molecule that overcomes HdmX-mediated p53 repression. CTX1 binds directly to HdmX to prevent p53-HdmX complex formation, resulting in the rapid induction of p53 in a DNA damage-independent manner. Treatment of a panel of cancer cells with CTX1 induced apoptosis or suppressed proliferation and, importantly, CTX1 demonstrates promising activity as a single agent in a mouse model of circulating primary human leukemia. CTX1 is a small molecule HdmX inhibitor that demonstrates promise as a cancer therapeutic candidate. Mol Cancer Ther; 15(4); 574-82. ©2016 AACR.