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Context: Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported. Case presentation and results: We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation). Post larotrectinib treatment, diagnostic I-123 whole body scan revealed unsuccessful RAI-uptake re-induction in the TERT-positive tumor, with a thyroid differentiation score (TDS) of −0.287. In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of −0.060. Conclusion: As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

[This corrects the article DOI: 10.3389/fimmu.2019.00040.].

Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.

Non-response is a common problem faced by surveyors while conducting surveys; this introduces a potential bias in the estimates of population parameters. One method of dealing with non-response is subsampling of the non-respondents, which increases precision in estimates by increasing the sample size. This study proposes an unbiased mean estimator in the presence of non-response using the Paired Ranked Set Sampling (PRSS) technique. The proposed estimator is based on a suggested strategy for adapting the subsampled units into the initial sample. Variance of the proposed estimator is derived, and conditions are provided for which the proposed estimator performs better than existing estimators. We conduct a simulation study to evaluate the precision of the proposed estimator in comparison with other existing estimators for estimating the population mean. In simulation, we assume populations based on normal distribution, exponential distribution, and real-life data on abalone. Simulation results show that the proposed mean estimator exhibits a higher probability of precisely estimating the finite population mean. [ABSTRACT FROM AUTHOR]

Background: Prehypertension is a preclinical state of hypertension which leads to an increased likelihood of coronary heart disease, myocardial infarction, cerebrovascular disease as well as target organ damage. Addressing pre-hypertension through early lifestyle interventions is crucial to mitigating these detrimental effects and improving long-term health outcomes. So, the main objective of this study is to develop a lifestyle intervention program (LSIP) for the management of prehypertension using consensus building approach. Methods: It was a three round online modified Delphi study with 70 members panellists. All panellists had an experience of prehypertension either as patients (n = 30) or professionals (n = 40). Round 1 included initial recommendations developed from a previous systematic review and metanalysis, which were rated by panellists for their importance on a 5-point Likert scale. Panellists could also suggest additional items in the Round 1. Round 2 and 3 included all items from the Round 1 with new items suggested by the panellists. Data was analysed descriptively using SPSS version 29. All items receiving at least 70% of all respondents combined rating of 'Important' and 'Very Important' in Round 3 were included in the final set of recommendations. Results: Fifty-one panellists (80.9%) (patients = 25, professionals = 26) completed Round 3. Twenty-six recommendation items were included in the Round 1. Twenty new items were added in Round 2 with 46 total items in Round 2 and 3. Thirty-five of these items reached consensus in Round 3. The final set of recommendation comprised of 15 educational. 10 dietary, and 10 exercise recommendations. Conclusion: This modified Delphi study developed a comprehensive LSIP for the prevention of prehypertension, incorporating a holistic approach with educational, dietary, and exercise components aimed at the general population. Previously established standards of care (SOC) for managing prehypertension varied significantly and often provided fragmented guidance particularly on physical activity and education. This preventive model offers a novel and scalable approach for early intervention in prehypertension, potentially reducing reliance on medications and improving long-term health outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Escala de Calidad de vida Osteoporosis (ECOS-16) was originally developed in Spanish to evaluate the quality of life (QoL) in post-menopausal women (PMW) with osteoporosis or osteopenia based on the osteoporosis-specific QoL instruments. ECOS-16 has been translated into several languages, but the Urdu version is not yet available. OBJECTIVE: To translate the ECOS-16 Questionnaire into Urdu and determine its validity and reliability in PMW with osteopenia. METHODS: This was a linguistic validity and reliability study. ECOS-16 was translated into Urdu using Beaton's guidelines. Content validity was examined using Waltz's four-point ordinal scale. Twenty osteopenia-afflicted PMW aged 48–70 underwent pilot testing for face validity. Discriminant validity was determined by an independent T-test between PMW women with and without osteopenia. Convergent validity was assessed using Spearman's correlation coefficient. Cronbach's alpha and Intraclass correlation coefficient (ICC2,1) assessed internal consistency and test-retest reliability. The factor analysis was used to describe the factors. RESULTS: Each question's content validity ratio (CVR) was 0.83–1.00, while the scale's S-CVR was 0.96. Each question's Likert scale content validity index (CVI) was 0.91–0.93, while the scale's S-CVI was 0.91. Significant discriminant validity was found between groups in weeks I and II (p -value < 0.001). A correlation coefficient of 0.89 and 0.96 (p -value < 0.001) between Urdu ECOS-16 total score and SF-36 and EQ-5D scores suggests convergent validity. One component explained 83.86% of Urdu ECOS-16's variance in factor analysis. Excellent test-retest reliability (ICC2,1 = 0.990, 95% CI, 0.985–0.994, p -value < 0.001). Cronbach's alpha for standardized items was 0.995. CONCLUSION: ECOS-16 translated in Urdu is a valid and reliable questionnaire to assess QoL in PMW with osteopenia. It has a simple and easy language that can be understood easily by the Urdu-speaking population. [ABSTRACT FROM AUTHOR]

Migraine (Mg) is a multifaceted neurovascular disorder caused by genetic and several environmental etiologies. We have implemented a case-control study of TNFα gene polymorphism in 212 Mg patients and 218 healthy controls utilizing the ARMS-PCR technique, followed by Sanger sequencing. Besides, we have conducted a meta-analysis of different genetic models (five genetic models) to combine and summarize the available data from 11 studies (including this present research). The strength of genetic associations in the meta-analysis used to assess by the pooled odds ratio (OR) and 95% confidence intervals (CI). The results of this case-control study discovered a significant relationship with Mg in recessive and homozygous genotype with OR = 2.35 (95% CI [0.96–5.74]), p-value = 0.045. Also, the outcomes of meta-analysis suggested an irrelevant relationship between TNFα gene (rs1800629) polymorphism and Mg susceptibility in the five genetic models. However, subgrouping based on ethnic background showed a significant association in the allelic genetic model with OR = 1.53 (95% CI [1.02–2.31]), p = 0.040 respectively. The meta-analysis results of TNFα gene polymorphism may represent a risk factor for Mg among Asians. In the future, large scale, multicentric case-control study by classification of patients with Mg with or without aura can be performed worldwide to identify the potential genetic risk factors leading to Mg pathogenesis.

Soil erosion is a serious environmental problem faced by district Chakwal. Unpredictable short term and high intensity rainfall, improper cultivation and deforestation have accelerated the soil erosion in the district. The agricultural productivity of the study area can be enhanced by understanding, estimating and controlling the root causes of soil erosion. This study was undertaken to estimate and spatially represent the rate of average annual soil erosion in Chakwal using GIS/RS techniques. The soil erosion was estimated using Universal Soil Loss Equation (USLE) model. To find out parameters of USLE, ASTER GDEM of 30 m resolution was used to estimate slope length and elevation of the study area. Landsat 8 satellite imagery of year 2019, was used to prepare land use map using supervised classification. Soil map with texture and geomorphology was used to identify soils of study area and rainfall data of last 7 years was also studied. Finally, the soil loss has been computed using raster calculator of ArcGIS 10.2 software. The average annual soil loss was predicted up to 268,619 tons/acre/year, of which maximum soil erosion was occurring near the steep slopes and river channels. It is necessary to adapt sustainable land management practices to reduce the risk of further soil erosion, by adopting rainwater harvesting and choosing right crops for suitable soil type

Objective: To compare the effects of Intranasal Betamethasone and Beclomethasone in patients with Allergic Rhinitis. Study Design: Quasi experimental study. Place and Duration of Study: Combined Military Hospital Bahawalpur and Shahida Islam Medical and Dental College Lodhran, from Mar 2018 to Feb 2019. Methodology: A total of 200 patients who were between 22-55 years of age were included in this study. Half of them received Intranasal Betamethasone were compared with the other half who received Intranasal Beclomethasone. Clinical success was compared in both groups in terms of patients becoming a symptomatic. Results: Clinical symptoms were markedly reduced in both groups at the end of the study as 94 (94%) and 78 (78%) of patients who were on Intranasal Betamethasone and Intranasal Beclomethasone respectively showing that Intranasal Betamethasone is superior to Intranasal Beclomethasone in controlling Allergic Rhinitis symptoms. Chi square test is applied and p-value calculated (p=0.045) significant. Conclusion: Intranasal Betamethasone is far more effective drug as compare to Intranasal Beclomethasone in controlling allergic symptoms.

Key Clinical Message: Despite being generally treatable and preventative, pulmonary tuberculosis (PTB) is one of the most common infectious agents that cause death. Misdiagnosis of TB frequently leads to unwarranted diagnostic procedures and postpones the start of treatment. Pulmonary tuberculosis (PTB) can present with various unusual radiological and clinical characteristics. Misdiagnosis of TB frequently leads to unwarranted diagnostic procedures and postpones the start of treatment. Here, we describe a 50‐year‐old man who presented with a cancerous‐type lesion on radiological findings and atypical symptoms that led to an initial diagnosis of lung cancer. However, histopathology and biopsy of the lung lesion revealed chronic granulomatous inflammation with caseous necrosis, confirming PTB as the true cause, with no further indications of malignancy. [ABSTRACT FROM AUTHOR]

Land use and land cover changes (LULCCs) are vital indicators for assessing the dynamic relationship between humans and nature, particularly in diverse and evolving landscapes. This study employs remote sensing (RS) data and machine learning algorithms (MLAs) to investigate LULCC dynamics within the Indus River Delta region of Sindh, Pakistan. The focus is on tracking the trajectories of land use changes within mangrove forests and associated ecosystem services over twenty years. Our findings reveal a modest improvement in mangrove forest cover in specific areas, with an increase from 0.28% to 0.4%, alongside a slight expansion of wetland areas from 2.95% to 3.19%. However, significant increases in cropland, increasing from 22.76% to 28.14%, and built-up areas, increasing from 0.71% to 1.66%, pose risks such as altered sedimentation and runoff patterns as well as habitat degradation. Additionally, decreases in barren land from 57.10% to 52.7% and a reduction in rangeland from 16.16% to 13.92% indicate intensified land use conversion and logging activities. This study highlights the vulnerability of mangrove ecosystems in the Indus Delta to agricultural expansion, urbanization, resource exploitation, and land mismanagement. Recommendations include harmonizing developmental ambitions with ecological conservation, prioritizing integrated coastal area management, reinforcing mangrove protection measures, and implementing sustainable land use planning practices. These actions are essential for ensuring the long-term sustainability of the region's ecosystems and human communities. [ABSTRACT FROM AUTHOR]

Background: Osteopenia, caused by estrogen deficiency in postmenopausal women (PMW), lowers Bone Mineral Density (BMD) and increases bone fragility. It affects about half of older women's social and physical health. PMW experience pain and disability, impacting their health-related Quality of Life (QoL) and function. This study aimed to determine the effects of Kinect-based Virtual Reality Training (VRT) on physical performance and QoL in PMW with osteopenia. Methodology: The study was a prospective, two-arm, parallel-design, randomized controlled trial. Fifty-two participants were recruited in the trial, with 26 randomly assigned to each group. The experimental group received Kinect-based VRT thrice a week for 24 weeks, each lasting 45 min. Both groups were directed to participate in a 30-min walk outside every day. Physical performance was measured by the Time Up and Go Test (TUG), Functional Reach Test (FRT), Five Times Sit to Stand Test (FTSST), Modified Sit and Reach Test (MSRT), Dynamic Hand Grip Strength (DHGS), Non-Dynamic Hand Grip Strength (NDHGS), BORG Score and Dyspnea Index. Escala de Calidad de vida Osteoporosis (ECOS-16) questionnaire measured QoL. Both physical performance and QoL measures were assessed at baseline, after 12 weeks, and after 24 weeks. Data were analyzed on SPSS 25. Results: The mean age of the PMW participants was 58.00 ± 5.52 years. In within-group comparison, all outcome variables (TUG, FRT, FTSST, MSRT, DHGS, NDHGS, BORG Score, Dyspnea, and ECOS-16) showed significant improvements (p < 0.001) from baseline at both the 12th and 24th weeks and between baseline and the 24th week in the experimental group. In the control group, all outcome variables except FRT (12th week to 24th week) showed statistically significant improvements (p < 0.001) from baseline at both the 12th and 24th weeks and between baseline and the 24th week. In between-group comparison, the experimental group demonstrated more significant improvements in most outcome variables at all points than the control group (p < 0.001), indicating the positive additional effects of Kinect-based VRT. Conclusion: The study concludes that physical performance and QoL measures were improved in both the experimental and control groups. However, in the group comparison, these variables showed better results in the experimental group. Thus, Kinect-based VRT is an alternative and feasible intervention to improve physical performance and QoL in PMW with osteopenia. This novel approach may be widely applicable in upcoming studies, considering the increasing interest in virtual reality-based therapy for rehabilitation. [ABSTRACT FROM AUTHOR]