A network meta-analysis of the association between patient traits and response to regular dosing with ICS plus short-acting ß2-agonist reliever or ICS/formoterol reliever only in mild asthma.

INTRODUCTION/BACKGROUND: Mild asthma treatment recommendations include intermittent inhaled corticosteroid (ICS)/formoterol dosing or regular ICS dosing with short-acting ß2-agonist reliever. Due to the heterogeneity of asthma, identification of traits associated with improved outcomes to specific treatments would be clinically beneficial. AIMS/OBJECTIVES: To assess the impact of patient traits on treatment outcomes of regular ICS dosing compared with intermittent ICS/formoterol dosing, a systematic literature review (SLR) and network meta-analysis (NMA) was conducted. Searches identified randomised controlled trials (RCTs) of patients with asthma aged ≥12 years, containing ≥1 regular ICS dosing or intermittent ICS/formoterol dosing treatment arm, reporting traits and outcomes of interest. RESULTS: The SLR identified 11 RCTs of mild asthma, of 14,516 patients. A total of 11 traits and 11 outcomes of interest were identified. Of these, a feasibility assessment indicated possible assessment of three traits (age, baseline lung function, smoking history) and two outcomes (exacerbation rate, change in lung function). The NMA found no significant association of any trait with any outcome with regular ICS dosing relative to intermittent ICS/formoterol dosing. Inconsistent reporting of traits and outcomes between RCTs limited analysis. CONCLUSIONS: This is the first systematic analysis of associations between patient traits and differential treatment outcomes in mild asthma. Although the traits analysed were not found to significantly interact with relative treatment response, inconsistent reporting from the RCTs prevented assessment of some of the most clinically relevant traits and outcomes, such as adherence. More consistent reporting of respiratory RCTs would provide more comparable data and aid future analyses.

Adiponectin and HbA1c levels among Indian patients with diabetes mellitus.

Adiponectin is closely related to glucose metabolism and newly diagnosed type 2 diabetes mellitus (T2DM), and other kinds of diabetes linked to the risk of T2DM. Therefore, it is of interest to report the correlation between adiponectin levels and glycosylated hemoglobin (HbA1c) as a diagnostic marker of T2DM and healthy control. Total 210 participants were included of IPD & OPD healthy controls with glycosylated hemoglobin levels under 6% were included. Blood samples, collected using sterile clot activator or plain vials, were stored at -20°C. The biomarker score that comprised significant differences in age, gender distribution, and metabolic indicators are seen between the diabetes (n=105) and control (n=105) groups. Increase in both Adiponectin and HbA1c% Mean±SD (6.86±0.23, p<0.0001; 22.71±2.01; p<0.0001) is indicative of deteriorating glycaemic control and an accompanying rise in inflammatory response. Positively correlate adiponectin levels with HbA1c levels (r2=0.398; p<0.0001), suggesting a link between inflammatory response and glucose control. Lower adiponectin levels are statistically associated with diabetes. Diabetes and adiponectin were negatively correlated and positive linear relationship between HbA1c and adiponectin levels. Adiponectin may be a significant factor useful in understanding the pathophysiology; they are likely to be straight forward instruments for predicting future risk of diabetes.

Comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements.

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (κ) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision of κ. These results revealed that systematic detector effects resulted in decreased accuracy and precision of κ in the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.

Genetic diversity, population structure analysis and codon substitutions of Indicine Badri cattle using ddRAD sequencing.

The present study was carried out on 96 animals representing three distinct colour variants of Badri cattle to investigate the genetic diversity, population structure and substitution mutations in the genetic codons due to single nucleotide variations. The DNA samples of 96 Badri cows were genotyped using a double digestion restriction associated DNA (ddRAD) sequencing approach. A standardized bioinformatics pipeline was employed to identify single nucleotide polymorphisms (SNPs), initially detecting 7,168,552 SNPs through alignment with the Bos indicus reference genome assembly. Subsequent stringent quality filtration yielded 65,483 high-confidence SNPs for downstream analysis. Genetic diversity analysis of the Badri cattle population resulted in average values of 0.145, 0.088, and 0.091 for Shannon's diversity Index (I), Simpson's Diversity (h), and Simpson's Unbiased Diversity (uh), respectively. Genetic similarities between the black and brown, black and grey, and brown and grey Badri variants were found to be 0.9972, 0.9980 and 0.9970, respectively. Tajima's D diversity value was observed to be significant and positive for 99.29% of high-confidence SNPs (65,483). STRUCTURE analysis showed admixture among the three Badri colour variants, suggesting a lack of genetic differentiation. Annotation of high-confidence SNPs regarding genetic codon changes indicated maximum substitutions in the GGC with GGT (22 occurrences), followed by AAC to AGC (20 occurrences), GAA to TAA (19 occurrences) and CAA to CAG (19 occurrences). The study concludes there are genetic similarities among colour variants, lack of rare alleles, balancing selection, sudden population contraction and genetic codon substitutions within the Badri cattle population. Insights derived from SNP data analysis hold potential significance for conservation initiatives and breed improvement programs for indicine cattle.

Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting ß2-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.

INTRODUCTION: Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting ß2-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted. METHODS: Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis. RESULTS: The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV1, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs. CONCLUSION: A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

Anatomical Modeling and Optimization of Speckle Contrast Optical Tomography.

Traditional methods for mapping cerebral blood flow (CBF), such as positron emission tomography and magnetic resonance imaging, offer only isolated snapshots of CBF due to scanner logistics. Speckle contrast optical tomography (SCOT) is a promising optical technique for mapping CBF. However, while SCOT has been established in mice, the method has not yet been demonstrated in humans - partly due to a lack of anatomical reconstruction methods and uncertainty over the optimal design parameters. Herein we develop SCOT reconstruction methods that leverage MRI-based anatomical head models and finite-element modeling of the SCOT forward problem (NIRFASTer). We then simulate SCOT for CBF perturbations to evaluate sensitivity of imaging performance to exposure time and SD-distances. We find image resolution comparable to intensity-based diffuse optical tomography at superficial cortical tissue depth (~1.5 cm). Localization errors can be reduced by including longer SD-measurements. With longer exposure times speckle contrast decreases, however, noise decreases faster, resulting in a net increase in SNR. Specifically, extending exposure time from 10µs to 10ms increased SCOT SNR by 1000X. Overall, our modeling methods provide anatomically-based image reconstructions that can be used to evaluate a broad range of tissue conditions, measurement parameters, and noise sources and inform SCOT system design.

Validation of secretory Immunoglobulin A (IgA) for early and efficient diagnosis of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa is a gram-negative bacterium that is considered to be a major causal organism of nosocomial infection. This study brought data-specific evidence to reveal the efficacy of secretory Immunoglobulin A (IgA) measurement in diagnosing pulmonary P. aeruginosa infection and claims its validation as a diagnostic marker. This study has included controls and patients of Pseudomonas and grouped them into four, namely, controls, chronic cases, intermittent cases, and negative group. The last group, that is, the "Negative" group, is the ones who had a history of infection but currently showed negative blood culture. The level of sIgA was quantified in all the patients and the controls and then their status of pulmonary infection was determined by their blood culture. ANOVA and Pearson Chi-Square were employed for showing the association between sIgA and pulmonary infection. The mean value of salivary sIgA has been found the highest in chronic cases followed by Intermittent cases and Negative Infections. The boxplot diagram showed several parameters of sIgA quantification in each group and control. ANOVA and Pearson Chi-square (P<0.005) tests showed a significant association between sIgA level in saliva and pulmonary infection of P. aeruginosa. The ROC curve was plotted to determine the cut-off value of sIgA (sIgA≧13.09 U/ml) for efficient clinical diagnosis of pulmonary P. aeruginosa infection. The study has validated statistically that quantification of salivary sIgA can be used in clinical practice for early diagnosis of pulmonary infection of P. aeruginosa.

A comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements.

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (κ) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision of κ. These results revealed that systematic detector effects resulted in decreased accuracy and precision of κ in the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.

Serum Expression Level of MicroRNA-122 and its Significance in different Stages of Hepatitis B Virus Infection.

This study aims to determine the serum expression level of miRNA-122 and its significance in the different stages of Hepatitis B virus infection. The study subjects were recruited and grouped for Hepatitis B associated with Chronic Hepatitis B infection, hepatic sclerosis, hepatocellular carcinoma, and healthy controls were also considered. Venous blood was collected from the participants including the controls and routine blood tests and quantification of miRNA-122 were done and analyzed in each case of hepatitis B infection and compared with that of healthy controls. The miRNA-122 was determined, which came to be highest in patients with Chronic Hepatitis B while patients with hepatic sclerosis and patients with hepatocellular carcinoma showed a subsequent number of copies. The number of copies of miRNA-122 in the CHB, hepatic sclerosis, and HCC group was significantly higher than in the healthy control. The quantification of miRNA-122 and subsequently plotting the ROC curve has shown that miRNA-122 can be considered as a biomarker of hepatitis B for screening and diagnosis purposes.

A network meta-analysis of the association between patient traits and response to regular dosing with ICS/long-acting ß2-agonist plus short-acting ß2 agonist reliever or maintenance and reliever therapy for asthma.

INTRODUCTION: Current treatment for moderate-severe asthma with inhaled corticosteroid (ICS)-based therapy can follow two strategies: a single inhaler maintenance and reliever therapy (MART) regimen, or regular dosing with ICS/long-acting ß2-agonist used as maintenance therapy plus a separate short acting ß2-agonist reliever inhaler. It would be clinically useful to understand the potential of patient traits to influence regular dosing or MART treatment outcomes. OBJECTIVES: A systematic literature review (SLR) and meta-analysis was conducted to identify specific patient traits that may predict improved clinical outcomes with regular dosing or MART. RESULTS: The SLR identified 28 studies in patients with moderate-severe asthma assessing regular dosing or MART treatments and reporting the traits and outcomes of interest. Network meta-regressions found no significant difference in the relative efficacy of regular dosing as compared with MART on any of the clinical outcomes (exacerbation rate, time to first exacerbation, FEV1, reliever use and adherence) for any of the patient traits (baseline lung function, baseline ACQ, age, BMI, and smoking history) evaluated. However, some trends towards traits influencing treatment efficacy were identified. Inconsistent reporting of traits and outcomes was observed between trials. CONCLUSIONS: The analysed patient traits evaluated in this study were associated with similar efficacy for the analysed outcomes to either regular dosing or MART; however, trends from the data observed encourage future analyses for possible identification of additional traits, or a combination of traits, that may be of interest. More comparable reporting of clinically important traits and outcomes would improve future analyses.

Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management.

INTRODUCTION: Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies. METHODS: We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios. RESULTS: A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence. CONCLUSION: In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Park Area and Physical Activity Among Children and Adolescents: Findings From the Healthy Communities Study.

BACKGROUND: There is currently a nationwide effort to bring parks and green spaces within a 10-minute walk of the home. We examined the association between park area within 1 km of a child's residence and self-reported park-specific physical activity (PA) along with accelerometer-derived moderate to vigorous physical activity (MVPA). METHODS: A subsample of K through eighth-grade youth (n = 493) from the Healthy Communities Study reported whether they engaged in park-specific PA during the last 24 hours and wore an accelerometer for up to 7 days. Park area was defined as the percentage of park land in a 1 km Euclidean buffer around the participant's residence, categorized into quintiles. Analysis consisted of logistic and linear regression modeling with interaction effects that controlled for clustering within communities. RESULTS: Regression models estimated greater park-specific PA for participants in the fourth and fifth quintiles of park land. Age, sex, race ethnicity, and family income were unrelated to park-specific PA. Accelerometer analysis indicated that total MVPA was unrelated to park area. Older children (ß = -8.73, P < .001) and girls (ß = -13.44, P < .001) engaged in less MVPA. Seasonality significantly predicted both park-specific PA and total MVPA. CONCLUSION: Increasing park area is likely to improve youth PA patterns, lending support for the 10-minute walk initiative.

Evaluation of Lung Functions, Blood Pressure, and Hearing Deterioration in Tile Setters.

INTRODUCTION: Tile setters in construction industries are exposed to a potent risk of silicosis as they are constantly exposed to crystalline silica dust during concrete finishing, cutting and fixing of the ceramic tiles. The noise produced by instruments used in tile settings may lead to noise-induced hearing loss. Noise above the permissible limit of 85 dB may lead to autonomic changes and alteration in blood pressure. These facts gave us an impetus to evaluate the pulmonary functions, blood pressure and hearing deterioration in tile setters and correlate these parameters for their present functional status with duration of exposure to tile cutting profession. METHODS: The pulmonary functions were evaluated with spirometer, autonomic status by recording the blood pressure and hearing loss by calculating the Hearing Deterioration Index (HDI) for hearing loss. RESULTS: There was significant decline in forced vital capacity (FVC), forced expiratory volume 1 sec (FEV1) and forced expiratory volume 1% (FEV1%) in tile setters. The decline in FVC, FEV1 and FEV1% was significantly higher in subjects with exposure of more than five years. There was increased systolic and diastolic blood pressure in those having more than five years of exposure in the tile setting profession as compared to less than five years. There was a positive correlation between years of service in the tile setting profession as well as sound exposure level with HDI and blood pressure in our subjects. CONCLUSION: Prolonged exposure to the tile setting profession may lead to compromised lung function, hypertension and hearing deterioration in tile setters.

Multi-mode fiber-based speckle contrast optical spectroscopy: analysis of speckle statistics.

Speckle contrast optical spectroscopy/tomography (SCOS/T) provides a real-time, non-invasive, and cost-efficient optical imaging approach to mapping of cerebral blood flow. By measuring many speckles (n>>10), SCOS/T has an increased signal-to-noise ratio relative to diffuse correlation spectroscopy, which measures one or a few speckles. However, the current free-space SCOS/T designs are not ideal for large field-of-view imaging in humans because the curved head contour cannot be readily imaged with a single flat sensor and hair obstructs optical access. Herein, we evaluate the feasibility of using cost-efficient multi-mode fiber (MMF) bundles for use in SCOS/T systems. One challenge with speckle contrast measurements is the potential for confounding noise sources (e.g., shot noise, readout noise) which contribute to the standard deviation measure and corrupt the speckle contrast measure that is central to the SCOS/T systems. However, for true speckle measurements, the histogram of pixel intensities from light interference follows a non-Gaussian distribution, specifically a gamma distribution with non-zero skew, whereas most noise sources have pixel intensity distributions that are Gaussian. By evaluating speckle data from static and dynamic targets imaged through an MMF, we use histograms and statistical analysis of pixel histograms to evaluate whether the statistical properties of the speckles are retained. We show that flow-based speckle can be distinguished from static speckle and from sources of system noise through measures of skew in the pixel intensity histograms. Finally, we illustrate in humans that MMF bundles relay blood flow information.

Genome-wide identification and annotation of SNPs and their mapping in candidate genes related to milk production and fertility traits in Badri cattle.

This study was conducted in Badri cattle using a double digest restriction-site associated DNA sequencing approach. The study aimed to identify and annotate high confidence single nucleotide polymorphisms (SNPs) and their mapping in candidate genes related to production and fertility in dairy cattle. A total of 7,168,552 genome-wide SNPs were initially identified in Badri cattle by alignment with the Bos indicus reference genome. After filtration of SNPs, 65,483 high confidence SNPs were retained and further used for downstream analysis. Annotation of high confidence SNPs revealed 99.197% SNPs had modifier impact, 0.326% SNPs were low impact, 0.036% were high impact, and 0.441% were moderate impact SNPs. Most SNPs in Badri cattle were found in intergenic, transcript and intronic regions. The candidate genes for milk production PRKCE, ABCG2, GHR, EPS8, CAST and NRXN1 were found to harbour maximum high confidence variants. Among candidate genes for fertility in cattle, ATP2B1, SOX5, WDR27, ARHGAP12, CACNA1D, ANKRD6, GRIA3, ZNF521 and CAST822 have maximum high confidence variants mapped in them. The SNPs found mapped in the candidate genes will be important genetic tools in the search for phenotype-modifying nucleotide changes and will aid in formulating relevant genetic improvement programmes for dairy cattle.

Association of Autonomic Balance With Phone Call Duration in Healthy Individuals.

Background This study aimed to estimate the association of autonomic balance with the duration of phone calls in healthy individuals. Methodology A total of 30 subjects aged between 18 and 30 years without any established systemic disease and using mobile phones for more than five years with minimum daily usage of 30 minutes were included in this analytical study. Heart rate variability (HRV) was recorded using a three-channel physiograph (AD Instruments South Asia (India) Pvt. Ltd., New Delhi, India) with the software LabChart PROV8.1.8 with HRV Module version 2.0.3 for 10 minutes. Time domain parameters were recorded in terms of the standard deviation of normal to normal interval (SDNN), root mean square of successive differences between normal heartbeats (RMSSD), R-R intervals greater than 50 ms (pRR50), and mean heart rate (MHR), and frequency domain parameters were total power, low-frequency power (LF), high-frequency power (HF), and the ratio of low-frequency to high-frequency power (LF/HF). HRV was recorded three times in each subject that included baseline HRV, HRV during the use of a mobile phone, and HRV after the use of a mobile phone. Results A total of 30 subjects (14 males and 16 females) participated in this study. The mean age of participants was 31.93 ± 8.59 years (32.07 ± 9.87 years for males, and 31.81 ± 7.64 years for females). There were no findings of significant arrhythmia in any of the participants. There was a significant difference in pRR50 on comparing all three phases (p = 0.036). However, there was no significant variation in other parameters such as very low frequency (VLF, ms2), VLF (%), LF (ms2), LF (%), HF (ms2), HF (%), LF/HF, SDNN (ms), RMSSD (ms), Poincare plot standard deviation perpendicular to the line of identity (ms), Poincare plot standard deviation along the line of identity (ms), systolic blood pressure (mmHg), and diabolic blood pressure (mmHg) during, before, and after exposure to mobile phone calls. There was no significant difference in the value of all parameters between males and females (p < 0.05). Conclusions Mobile phone calls may influence HRV and autonomic balance. This change may be affected by the electromagnetic field and by speaking as well.

iPSC-Derived Neurons from Patients with POLG Mutations Exhibit Decreased Mitochondrial Content and Dendrite Simplification.

Mutations in POLG, the gene encoding the catalytic subunit of DNA polymerase gamma, result in clinical syndromes characterized by mitochondrial DNA (mtDNA) depletion in affected tissues with variable organ involvement. The brain is one of the most affected organs, and symptoms include intractable seizures, developmental delay, dementia, and ataxia. Patient-derived induced pluripotent stem cells (iPSCs) provide opportunities to explore mechanisms in affected cell types and potential therapeutic strategies. Fibroblasts from two patients were reprogrammed to create new iPSC models of POLG-related mitochondrial diseases. Compared with iPSC-derived control neurons, mtDNA depletion was observed upon differentiation of the POLG-mutated lines to cortical neurons. POLG-mutated neurons exhibited neurite simplification with decreased mitochondrial content, abnormal mitochondrial structure and function, and increased cell death. Expression of the mitochondrial kinase PTEN-induced kinase 1 (PINK1) mRNA was decreased in patient neurons. Overexpression of PINK1 increased mitochondrial content and ATP:ADP ratios in neurites, decreasing cell death and rescuing neuritic complexity. These data indicate an intersection of polymerase gamma and PINK1 pathways that may offer a novel therapeutic option for patients affected by this spectrum of disorders.