Comparative Evaluation of Er: YAG Laser, Diode Laser, and Novamin Technology for Dentinal Tubule Occlusion: An In-Vitro Scanning Electron Microscope (SEM) and Energy Dispersive X-Ray Analysis (EDX) Study.

BACKGROUND: Dentinal hypersensitivity is a brief and painful oral condition that is characterized by an abrupt shooting sensation. Stimulation occurs when hot, cold, sweet, or sour food comes into contact with exposed dentinal tubules. The present study used a scanning electron microscope (SEM) and energy dispersive X-ray analysis (EDX) to investigate the efficacy of Er: YAG, 810 nm diode LASER, and NovaMin Technology in obstructing dentinal tubules. MATERIAL AND METHODS: We extracted the outer layers of 30 human teeth to expose the tubules and then treated the surfaces with 17% ethylenediaminetetraacetic acid (EDTA) to create an etched effect. Three cohorts were created from the portions. Group A was subjected to the application of Erbium:Yttrium-Aluminum-Garnet (Er: YAG) laser with a power output of 2W in the non-contact mode for 1 minute. Group B was subjected to the application of an 810nm diode laser with a power output of 1W in continuous mode for 30 seconds. Group C was subjected to the application of NovaMin paste, which contains a 927 ppm fluoride content. Following the therapy, occluded dentinal tubules were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) for both quantitative and qualitative examination. The data analysis was conducted using a one-way analysis of variance (ANOVA) and Tukey's test, with a significance threshold of 0.05. RESULTS: The average percentages of complete blockage of dentinal tubules in Groups A, B, and C were evaluated using the number of entirely unobstructed dentinal tubules at magnifications of 2000X (F = 3.05, p = 0.064), 5000X (F = 5.33, p = 0.011), and 10000X (F = 8.63, p = 0.001). The count of partially open dentinal tubules seen at magnifications of 2000X, 5000X, and 10000X was F = 10.15 (P < 0.001), F = 5.97 (p = 0.007), and F = 2.12 (p = 0.140) accordingly. CONCLUSION: NovaMin technology has demonstrated more effectiveness in blocking dentinal tubules compared to 810nm diodes and Er: YAG lasers.

Antibiotic resistance genes prediction via whole genome sequence analysis of Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) is the first dominant ubiquitous bacterial species identified from the genus Stenotrophomonas in 1943 from a human source. S. maltophilia clinical strains are resistance to several therapies, this study is designed to investigate the whole genome sequence and antimicrobial resistance genes prediction in Stenotrophomonas maltophilia (S. maltophilia) SARC-5 and SARC-6 strains, isolated from the nasopharyngeal samples of an immunocompromised patient. METHODS: These bacterial strains were obtained from Pakistan Institute of Medical Sciences (PIMS) Hospital, Pakistan. The bacterial genome was sequenced using a whole-genome shotgun via a commercial service that used an NGS (Next Generation Sequencing) technology called as Illumina Hiseq 2000 system for genomic sequencing. Moreover, detailed in-silico analyses were done to predict the presence of antibiotic resistance genes in S. maltophilia. RESULTS: Results showed that S. maltophilia is a rare gram negative, rod-shaped, non sporulating bacteria. The genome assembly results in 24 contigs (>500 bp) having a size of 4668,850 bp with 65.8% GC contents. Phylogenetic analysis showed that SARC-5 and SARC-6 were closely related to S. maltophilia B111, S. maltophilia BAB-5317, S. maltophilia AHL, S. maltophilia BAB-5307, S. maltophilia RD-AZPVI_04, S. maltophilia JFZ2, S. maltophilia RD_MAAMIB_06 and lastly with S. maltophilia sp ROi7. Moreover, the whole genome sequence analysis of both SARC-5 and SARC-6 revealed the presence of four resistance genes adeF, qacG, adeF, and smeR. CONCLUSION: Our study confirmed that S. maltophilia SARC-5 and SARC-6 are one of the leading causes of nosocomial infection which carry multiple antibiotic resistance genes.

The Role of Osteogenic Effect and Vascular Function in Bone Health in Hypertensive Rats: A Study of Anti-hypertensive and Hemorheologic Drugs.

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.

Donor Safety First: Postoperative Hepatectomy Outcomes in Living Liver Donors.

BACKGROUND: Living donor liver transplantation (LDLT) has become a popular treatment option because some countries lack a deceased organ program and the growing demand for liver transplants. Although postoperative outcomes are similar to deceased donor liver transplants, there is still an element of risk to the donor. The Clavien-Dindo classification system has been used to standardize reporting across different institutions and surgeons to categorize surgical outcomes. METHODS: Between January 1, 2022, and December 31, 2022, 207 living donors underwent hepatectomies at our center. All donors underwent a 3-step process of mandatory screening. Postsurgical complications were classified using the Clavien-Dindo classification. RESULTS: A total of 207 donor hepatectomies for LDLT were performed during our study period. Most donors (92.8%) were aged between 18 and 39 years. The most common type of graft used was a right lobe without the middle hepatic vein (82.6%). Most donors (91.7%) experienced an intraoperative blood loss of ≤500 mL. A total of 140 patients had an ordinary postoperative course. Grade 1 complications were observed in 16.9%, grade 2 in 12.1%, and grade 3 in 3.4% of the remaining patients. No grade 4 or grade 5 (patient death) complications were observed in this cohort. CONCLUSIONS: Living donor liver transplantation remains the most practiced liver transplant surgery in Pakistan. Our findings highlight the safety of the LDLT program with minimal risk of significant complications. The study also underscores the importance of careful screening and monitoring of living donors and the need for standardized reporting of surgical outcomes using the Clavien-Dindo classification system.

Triple synchronous malignancies of the stomach, bladder and thyroid in a previously treated prostate cancer patient: A Case Report.

Cancers that develop within six months of the first primary cancer are referred to as synchronous malignancies. These malignancies are difficult to diagnose and treat, with treatment primarily based on case reports.

Stromal inflammation, fibrosis and cancer: An old intuition with promising potential.

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment. Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis. Chronic inflammation can promote tumorigenesis via growth factor/cytokine-mediated cellular proliferation, apoptotic resistance, immunosuppression; and free-radical-induced oxidative deoxyribonucleic acid damage. Fibrosis could cause a perturbation in the dynamics of the tumour microenvironment, potentially damaging the genome surveillance machinery of normal epithelial cells. In this review, we will provide an in-depth discussion of various diseases characterised by inflammation and fibrosis that have been associated with an increased risk of malignancy. In particular, we will present a comprehensive overview of the impact of alterations in stromal composition on tumorigenesis, induced as a consequence of inflammation and/or fibrosis. Strategies including the application of various therapeutic agents with stromal manipulation potential and targeted cancer screening for certain inflammatory diseases which can reduce the risk of cancer will also be discussed.

Assessing the Impact of a Health Education Intervention for Post-secondary International Students in Canada.

Objective The objective is to determine the impact of a health education intervention on self-rated health knowledge, levels of stress and anxiety, and ability to find and access school resources for international students studying at a Canadian University and College. Participants and setting This is a pre- and post-intervention survey. Undergraduate and graduate international students on the shared campus of Durham College and Ontario Tech University in Oshawa, Ontario were included. Interventions  International students participating in this study received two structured visits, scheduled two weeks apart. At the start of the first visit, students completed a baseline survey which included questions on self-rated health knowledge, stress levels, and ability to access school resources. At this visit, students received 30 minutes of structured health education from a registered nurse on the topics of sexual health and adult immunizations.  At the second visit, students received 30 minutes of structured teaching from the registered nurse on the topics of mental health, COVID-19, and campus resources. Upon the completion of this teaching, students completed a post-intervention survey with the same questions as the pre-survey, to gauge for changes related to the intervention. Results T-values were calculated for each survey item from the pre and post-survey. These t-values were used as the outcome measure to determine changes in health knowledge, stress levels, and ability to access resources following the intervention. In total, there were 202 participants. Statistical analysis showed significant t-values for all survey items in the pre- and post-analysis. Following the education intervention, the highest t-values were noted in self-rated sexual health knowledge (t-value 16.80, p < 0.001), ability to find and access school resources (t-value 16.14, p < 0.001), and current level of stress/anxiety in regard to being in a new country (t-value 14.04, p < 0.001). Conclusion Following a structured health education intervention, international students reported significant increases in self-rated health knowledge for specific topics, ability to find and access school resources, ability to get help for a mental health issue, and significant decreases in self-rated stress/anxiety. These results can support further exploration of health education in international student populations to ensure these students are adequately informed and supported when arriving in a new country.

Anatomical variations in living donors for liver transplantation-prevalence and relationship.

PURPOSE: Living donor liver transplantation (LDLT) is a widely accepted option to address the lack of a deceased liver program for transplantation. Understanding vascular and biliary anatomy and their variants is crucial for successful and safe graft harvesting. Anatomic variations are common, particularly in the right hepatic lobe. To provide evidence for screening potential liver transplant donors, the presence of vascular and biliary anatomic variations in Pakistan's preoperative assessment of transplantation donor candidates was explored. METHODS: This retrospective cross-sectional study evaluated the hepatic artery, portal vein, hepatic vein, and biliary variations in living liver donors. The study included 400 living liver donors; data were collected from March 2019 to March 2023. We used a CT scan and MRCP to assess the anatomical variations. RESULTS: The study examined 400 liver donors aged 18 to 53 years. Conventional arterial anatomy was the most common (65.8%), followed by replaced right hepatic artery (16%) and replaced left hepatic artery (10.8%). Conventional type 1 biliary anatomy was seen in 65.8% of cases. The dominant right hepatic vein was found in 13.3% of donors. There was a significant association between the prevalence of variant portal venous anatomy with variant biliary anatomy. CONCLUSION: Variations of the hepatic arterial, portal venous, and biliary systems are frequent and should be carefully evaluated while selecting a suitable living donor. A strong relationship between variant portal venous and biliary anatomy was found. These findings can aid in selecting suitable candidates and improving surgical planning for liver transplantation.

Foreign body aspiration presenting as a chronic lung disease: a unique finding in an elderly patient.

Foreign body aspiration is a serious clinical manifestation in the elderly and has a significant potential to cause life-endangering harm. In this unique report, we highlight the case of a seventy-year-old conscious male, who reported with complaints of chronic cough initially diagnosed as chronic bronchitis; however, on radiological examination, the infectious nidus was identified as a 5 cm long metallic nail in the right lower lung.

Roll of partial slip on Ellis nanofluid in the proximity of double diffusion convection and tilted magnetic field: Application of Chyme movement.

The current study aims to investigate the effect of partial slip conditions over double diffusion convection. The phenomenon is applied with the inclined magnetic flux of peristaltic flow on Ellis nanofluid model in an asymmetric channel. The fundamental differential equations are constructed and solved through lubrication approximation that gives the coupled system of ordinary differential equations. This resultant system is further solved numerically, and graphic representation are used to physically comprehend the flow quantity data. The whole procedure is carried out under the trapping mechanism by drawing contour streamlines. The knowledge gained from this work will be useful in the creation of intelligent magneto-peristaltic pumps for specific heat and medication delivery phenomena.

Sequential extraction of selected metals to assess their mobility, pollution status and health risk in roadside soil.

Assessment of the mobility and contamination of trace metals in the roadside soil is important to explore the environmental quality and potential risks to the public health. The contents of selected metals (Ca, Mg, Sr, K, Na, Li, Fe, Mn, Zn, Cu, Ag, Co, Ni, Cr, Cd and Pb) in the roadside soil collected from major highways/roadsides of Lahore, Pakistan were quantified employing mBCR sequential extraction. Among the metals, Ca, Sr and Na showed highest contribution in exchangeable fraction, Pb in the reducible fraction and K, Li, Fe, Ag, Ni, Cu and Cr in the residual fraction. However, Mg and Mn exhibited relatively higher contents in exchangeable and residual fractions while Cd, Co and Zn showed relatively higher concentration in all four fractions. Comparatively higher mobility and availability in the soil was shown by Ca followed by Sr, Pb, Na, Cd, Zn, Co, Mn, Cu, Ag and Ni. Principal component analysis demonstrated considerable anthropogenic contributions of the trace metals in the roadside soil. The pollution indices showed that the soil was heavily to extremely polluted by Cd and Ag, followed by significant to very high contamination for Co, Ni and Pb. The modified degree of contamination (4.60 and 3.99 in summer and winter, respectively) revealed an overall high degree of contamination. The health risk assessment revealed that the calculated risks were within the safe limit thereby indicating insignificant non-carcinogenic and carcinogenic heath risk to the populace.

Does excessive energy utilization and expansion of urbanization increase carbon dioxide emission in Belt and Road economies?

The phenomenal increase in global temperature and variation in climate change are the replications of nature, alarming governments to limit the emissions of greenhouse gases (GHGs) and adopt green innovation and environmental-friendly clean and green technologies. In this paper, we empirically investigate whether there are any changes in excessive consumption of energy from conventional sources, expansion of urbanization, carbon dioxide (CO2) emissions, and economic growth in six different regions, namely, East Asia (EA), South Asia (SA), Southeast Asia (SEA), Central Asia (CA), Eastern Europe (EE), and the Middle East and North Africa (MENA), under the Belt and Road Initiatives of panel data over the period of 1985 to 2017. The empirical methods include a panel co-integration check, heterogeneity test, panel Granger causality test, pooled mean group (PMG), and augmented mean group (AMG). To verify the outcomes, robustness tests were carried out using the fully modified ordinary least squares (FMOLS) and dynamic ordinary least squares (DOLS) approaches. Our results confirm that CO2 emissions are primarily influenced by excessive utilization of conventional energy, economic growth, and expansion of urbanization. The findings confirm the co-integrating relationships among the variables in all six regions. Moreover, the panel causality analysis identified a bidirectional causal relationship between energy consumption, economic growth, urbanization, and CO2 emissions. While these results can play an instrumental role in formulating CO2 emission policies among our selected countries, our research can also assist policymakers and governments in other developing countries implement important policy initiatives. In this regard, the findings suggest that the current environment-related polices of Belt and Road Initiatives (BRI) do not efficiently tackle CO2 emissions. In order to achieve the CO2 emission degradation objective, the Belt and Road countries should restructure their environment-related policies by limiting the consumption of conventional energy and expansion of urbanization. The adaptation and establishment of such a panoramic policy program can assist emerging economies to acquire consolidated and environmentally sustainable economic growth.

Consumption of energy from conventional sources a challenge to the green environment: evaluating the role of energy imports, and energy intensity in Australia.

Conventional energy consumption such as coal, natural gas, and oil is a source of deteriorating environmental sustainability as well as a severe challenge to the green environment. The present paper explores the nexus between CO2 emissions, energy imports, energy intensity, and power generation from renewable and non-renewable energies from 1990 to 2021 in Australia. Based on the ARDL model, the findings reveal that energy imports and power generation from non-renewable energy sources show an adverse effect on the green environment. A 1% increase in conventional energy imports leads to an 11% increase in CO2 emissions. Similarly, a 1% increase in energy generation from conventional sources will increase CO2 emissions by 45%. On the other hand, lower energy intensity and power generation from renewable sources reveal a positive effect on environmental quality. A 1% increase in energy intensity will decrease CO2 emissions by 92% while energy generation from non-conventional sources by 15%. Most interestingly, energy intensity reveals the foremost position among all the selected variables to decarbonize and effectively transform conventional energy to clean and green energy production and utilization. The robustness test outcomes confirm the results of the empirical output. Furthermore, this study suggests that governments and policymakers should focus on the adaptation of lower energy intensity for the purpose to reduce CO2 emissions and promote a clean and green environment. Finally, power generation from renewable energy sources plays an inevitable role which ultimately helps environmentally sustainability in Australia.

Mobility, bioaccessibility, pollution assessment and risk characterization of potentially toxic metals in the urban soil of Lahore, Pakistan.

The present study is based on the measurement of potentially toxic metal contents employing various extraction methodologies aimed at the evaluation of their mobility, bioaccessibility and bioavailability in the urban soil (n = 56) of Lahore, Pakistan. Selected metal levels in the soil were quantified using flame atomic absorption spectrometry. On the average basis, aqua regia and glycine extracts revealed comparatively higher contents for most of the metals; average concentrations of Fe, Mn, Zn, Pb, Cu, Cr, Co and Cd were found at 1566, 451.1, 114.8, 52.84, 39.15, 24.82, 12.59 and 3.953 mg/kg in aqua regia extract, while in glycine extract the metal levels were found at 579.6, 174.2, 74.72, 49.74, 19.28, 7.103, 4.692 and 3.357 mg/kg, respectively. However, Cd, Pb, Cu and Zn showed significantly higher mobility and bioavailability in the soil, while Co, Fe and Mn were least mobile/bioavailable. The pollution index was assessed in terms of enrichment factor and modified degree of contamination which revealed severe to significant contamination and anthropogenic enrichment of Cd, Pb, Cu and Zn. Multivariate analysis showed mostly anthropogenic contributions for Zn-Cu-Cr-Pb-Cd. Health risk assessment revealed relatively higher exposure of the metals through ingestion, while only minor contributions were noted for inhalation and dermal contact. Hazard quotient index was within the safe limit (< 1.0) in all soil extractions, thereby indicating no significant non-carcinogenic health risks. The incremental lifetime cancer risk for Cr (4.1E-06) through ingestion was comparatively higher than the safe limit which showed significant lifetime cancer risk to the local population.

Carbon neutrality challenges in Belt and Road countries: what factors can contribute to CO2 emissions mitigation?

As climate warming is intensifying, CO2 emission reduction has aroused the great attention of many governments and scholars. Compared with traditional industrial times, the influencing system of CO2 emission in modern society has taken great changes due to technological advancement, improvement in energy efficiency, and the popularity of the internet. But the current literature has not reached a consensus on this theme. Our study tends to investigate the nexus between international trade, international trade taxes, energy intensity, internet usage, renewable energy, and CO2 emission while incorporating income levels by using the data from Belt and Road countries in the 2008-2020 period. For this purpose, we applied the unit root test, CSD, Granger causality test, AMG, CCMG, and CS-ARDL methods. The results show that energy efficiency, GDP, and internet use have significantly negative effects on CO2 emission, while GDP has significant positive impacts on CO2 emission. By classifying 65 countries along Belt and Road into four groups of low-income level, low-middle income level, upper-middle income level, and a high-income level, the regional heterogeneities of influencing factors of CO2 emission is confirmed. Furthermore, this empirical study provides new insights to policymakers to reduce CO2 emissions through technology innovation, international cooperation, and human capital investment without deteriorating economic growth.

Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study.

PURPOSE: To assess efficacy and toxicity of combination immunotherapy with ipilimumab plus nivolumab in routine practice in a retrospective multicentre cohort of patients with advanced melanoma. PATIENTS AND METHODS: This retrospective analysis included patients with advanced melanoma treated with ipilimumab and nivolumab between October 2015 and January 2020 at six centres in Australia, Europe and the United States of America. We describe efficacy outcomes (overall survival [OS], progression-free survival [PFS] and objective response rate [ORR]) in treatment-naïve and pre-treated patients, with and without brain metastases, plus treatment-related adverse events (trAEs) in all patients treated. RESULTS: A total of 697 patients were identified; 472 were treatment-naïve of which 138 (29.2%) had brain metastases, and 225 were previously treated of which 102 (45.3%) had brain metastases. At baseline, 32.3% had stage M1c and 34.4% stage M1d disease. Lactate dehydrogenase was high in 280 patients (40.2%). With a median follow-up of 25.9 months, median OS in the 334 treatment-naïve patients without brain metastases was 53.7 months (95% confidence interval [CI] 40.8-NR) and 38.7 months (95% CI 18.6-NR) for the 138 treatment-naïve patients with brain metastases. For the entire cohort the ORR was 48%, for treatment-naïve patients without brain metastases ORR was 56.6% with a median PFS of was 13.7 months (95% CI 9.6-26.5). Median PFS was 7.9 months (95% CI 5.8-10.4) and OS 38 months (95% CI 31-NR) for the entire cohort. Grade 3-4 trAE were reported in 44% of patients, and 4 (0.7%) treatment-related deaths (1 pneumonitis, 2 myocarditis and 1 colitis) were recorded. CONCLUSION: The outcome and toxicity of combination immunotherapy with ipilimumab and nivolumab in a real-world patient population are similar to those reported in pivotal trials.

Environmental regulations, political risk and consumption-based carbon emissions: Evidence from OECD economies.

The staggering rise in global temperature and abrupt change of climate are the responses of nature alerting humanity to limit the emissions of hazardous gases and adopt environmentally-benign life style. The present study explores empirically whether any changes in environmental policy stringency (EPSI), political risk (PR), and the interaction term of EPSI*PR result in any alteration of consumption-based carbon emissions (CBCE) of the 24 advanced OECD economies over the period of 1990-2020. Prior to the empirical estimations, various diagnostic tests are employed. The empirical techniques include, panel cointegration check, Cross-sectional Augmented Autoregressive Distributed Lags (CS-ARDL), and Dumitrescu & Hurlin panel causality test. The findings confirm that imports, gross domestic product, and stringency of environment policies activate CBCE in short-run. Whereas, a unit improvement in political risk and its interaction with environmental policy stringency give rise to 0.231 MtCO2 of CBCE in long run. Interestingly, the squared term of environmental policy stringency effectively tackles such emissions. Based on the findings, we conclude that the present environment related policies of OECD member states does not effectively limit CBCE. In order to achieve genuine emissions reduction goals, the selected nations should restructure their environment related policies by prioritizing increments in environmental policy stringency along with minimizing the risks involved in the political system.

Effects of Double Diffusive Convection and Inclined Magnetic Field on the Peristaltic Flow of Fourth Grade Nanofluids in a Non-Uniform Channel.

This study explored the impact of double diffusive convection and inclined magnetic field in nanofluids on the peristaltic pumping of fourth grade fluid in non-uniform channels. Firstly, a brief mathematical model of fourth grade fluid along inclined magnetic fields and thermal and concentration convection in nanofluids was developed. A lubrication approach was used to simplify the highly non-linear partial differential equations. An analytical technique was then used to solve the highly non-linear differential equations. The exact solutions for the temperature, nanoparticle volume fraction and concentration were calculated. Numerical and graphical outcomes were also examined to see the effects of the different physical parameters of the flow quantities. It was noted that as the impact of Brownian motion increased, the density of the nanoparticles also increased, which led to an increase in the nanoparticle fraction. Additionally, it could be observed that as the effects of thermophoresis increased, the fluid viscosity decreased, which lowered the fraction of nanoparticles that was made up of less dense particles.

Understanding COVID-19 Vaccine Hesitancy Through an Organizational Behaviour Lens.

Vaccine hesitancy during the COVID-19 pandemic has been a worldwide public health challenge. Organizational behaviour, the study of people's behaviours in organizational settings, can be used to identify the behavioural drivers contributing to vaccine hesitancy and to develop targeted strategies to combat those drivers and improve vaccine uptake. Some common behaviours driving vaccine hesitancy arise from individualism, motivation, attitude, perception, groupthink, heuristics and cognitive bias. Organizational behaviour strategies to combat vaccine hesitancy include fostering a collectivist attitude, overcoming personal barriers to communication such as individual beliefs and values, utilizing motivation theories to target the individualistic mindset, and overcoming attitudes and perceptions by addressing heuristics and cognitive biases.

NPHP3 splice acceptor site variant is associated with infantile nephronophthisis and asphyxiating thoracic dystrophy; A rare combination.

Nephronophthisis (NPHP) is a group of rare inherited ciliopathy disorders characterized by the multicystic dysplastic kidney, oligohydramnios, and tubulointerstitial nephritis that progresses to end-stage renal disease (ESRD). NPHP is a clinically and genetically heterogeneous disorder with extrarenal symptoms including skeletal deformities, nervous system anomalies, and ophthalmologic features. Three clinical subtypes, infantile, juvenile, and adolescent, have been recognized based on age of onset of ESRD. Infantile nephronophthisis with asphyxiating thoracic dystrophy is a very rare association. Here, we investigated a consanguineous family having two neonates with a clinical phenotype of lethal infantile NPHP associated with asphyxiating thoracic dystrophy. Whole exome sequence data analysis identified a splice acceptor site variant (Chr3-132408107-CCT-C; NM_153240.4: c.2694-2_2694-1del) in the NPHP3 gene. The segregation of a variant in the family was confirmed by Sanger sequencing. The lethal phenotype in our case might be due to respiratory insufficiency secondary to a severely restricted thoracic cage. Present work is an exclusive depiction of lethal infantile NPHP phenotype in association with asphyxiating thoracic dystrophy that has not been reported before in families segregating NPHP3 mutations. Moreover, this work expands the phenotypic spectrum of NPHP3 variants. Overall, our findings add to the increasing body of evidence that mutations in ciliary genes/proteins show pleiotropic effects with phenotypic overlap between related disorders and apparently unrelated clinical entities.