Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 107
Filter
1.
J Behav Med ; 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735024

ABSTRACT

Purpose We aimed to document the acceptability (enrollment rate) and feasibility (phone call delivery rate) of implementing a behavioral PA intervention over 12 weeks, in addition to documenting its effects on patient-reported outcomes and physical functioning. This study also describes the costs of carrying out a behavioral PA intervention. A total of 40 participants were randomized in a 1:1 ratio. The tailored behavioral PA intervention was developed based on the most recent PA guidelines in pediatric oncology and on the COM-B framework to enact PA behavior changes. The prescription (frequency, intensity, time and type (FITT)) was adjusted each week during the weekly support calls. The control group did not receive the intervention. 26 males and 14 females (13.6 years old on average and 2.9 years post-cancer treatment on average) participated in our study. The acceptability rate was 90.9% and the feasibility rate was > 85%. We found that 85% improved PA frequency, 80% improved PA intensity, 100% improved PA time, and 50.0% achieved the recommended PA guidelines. No adverse events were reported over the duration of the intervention. Physical function improved with longer 6-minute walk distances in the intervention group (465.8 ± 74.5 m) than in the control group (398.7 ± 92.9 m) (p = 0.016). PROs scores for all participants were within the limits of the normal range. The estimated cost per participant of carrying out this intervention was USD $126.57. Our 12-week behavioral PA intervention, based on the COM-B framework, was found to be acceptable, feasible and safe in childhood cancer survivors. This study is an important step in the right direction to make exercise standard practice in pediatric oncology.

2.
Cell Biochem Biophys ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594547

ABSTRACT

The Disabled-2 (DAB2) protein, found in 80-90% of various tumors, including breast cancer, has been identified as a potential tumor suppressor protein. On the contrary, some hypothesis suggests that DAB2 is associated with the modulation of the Ras/MAPK pathway by endocytosing the Grb/Sos1 signaling complex, which produces oncogenes and chemoresistance to anticancer drugs, leading to increased tumor growth and metastasis. DAB2 has multiple functions in several disorders and is typically under-regulated in several cancers, making it a potential target for treatment of cancer therapy. The primary function of DAB2 is the modulation of transforming growth factor- ß (TGF-ß) mediated endocytosis, which is involved in several mechanisms of cancer development, including tumor suppression through promoting apoptosis and suppressing cell proliferation. In this review, we will discuss in detail the mechanisms through which DAB2 leads to breast cancer and various advancements in employing DAB2 in the treatment of breast cancer. Additionally, we outlined its role in other diseases. We propose that upregulating DAB2 could be a novel approach to the therapeutics of breast cancer.

3.
Langmuir ; 40(15): 7835-7842, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38574181

ABSTRACT

Here, we compare the amount and morphology of silver (Ag) nanostructures electrodeposited at varied potentials and times in the presence of cetyltrimethylammonium bromide (CTAB) onto glass/indium tin oxide (glass/ITO) electrodes functionalized with mercaptopropyltrimethoxysilane (MPTMS) and coated or not coated with 4 nm average diameter Au nanoparticle (Au NP) seeds. There is a significantly larger amount of Ag deposited on the seeded electrode surface compared to that in the nonseeded electrode at potentials of -150 to -300 mV (vs Ag/AgCl) since the Au NP seeds act as catalysts for Ag deposition. At more negative overpotentials of -400 to -500 mV, the amount of Ag deposited on both electrodes is similar because the deposition kinetics are fast enough on glass/ITO that the Au seed catalyst does not make as big of a difference. Ag nanorods (NRs) and nanowires (NWs) form on the seeded surfaces, especially at more positive potentials, where deposition primarily occurs on the Au seed catalysts. Deposition of Ag onto the Au seeds appears as a separate peak in the voltammetry. This procedure mimics the seed-mediated growth of Ag NRs observed in solution in the presence of CTAB using ascorbic acid as a reducing agent. The yield, length, and aspect ratio of the Ag NRs/NWs depend on the deposition time and potential with the average length ranging from 300 nm to 3 µm for times of 30-120 min and potentials of -150 to -200 mV. The electrochemical seed-mediated growth of Ag NRs/NWs across electrode gaps could find use for resistive and surface-enhanced Raman-based sensing and molecular electronic applications.

4.
Cells ; 13(6)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38534348

ABSTRACT

The integration of whole genome sequencing (WGS) into all aspects of modern medicine represents the next step in the evolution of healthcare. Using this technology, scientists and physicians can observe the entire human genome comprehensively, generating a plethora of new sequencing data. Modern computational analysis entails advanced algorithms for variant detection, as well as complex models for classification. Data science and machine learning play a crucial role in the processing and interpretation of results, using enormous databases and statistics to discover new and support current genotype-phenotype correlations. In clinical practice, this technology has greatly enabled the development of personalized medicine, approaching each patient individually and in accordance with their genetic and biochemical profile. The most propulsive areas include rare disease genomics, oncogenomics, pharmacogenomics, neonatal screening, and infectious disease genomics. Another crucial application of WGS lies in the field of multi-omics, working towards the complete integration of human biomolecular data. Further technological development of sequencing technologies has led to the birth of third and fourth-generation sequencing, which include long-read sequencing, single-cell genomics, and nanopore sequencing. These technologies, alongside their continued implementation into medical research and practice, show great promise for the future of the field of medicine.


Subject(s)
Genomics , Precision Medicine , Infant, Newborn , Humans , Genomics/methods , Whole Genome Sequencing , Precision Medicine/methods , Pharmacogenetics , Genome, Human
5.
Cureus ; 16(2): e54940, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38544578

ABSTRACT

Background Infertility remains a significant global challenge, and recurrent implantation failure (RIF) poses a considerable concern in assisted reproductive technology. Understanding the factors contributing to implantation failure is essential for developing accurate diagnostic tools and treatment strategies. Endometrial receptivity (ER) during the window of implantation is crucial for successful embryo implantation in in vitro fertilization (IVF) procedures. Molecular-based endometrial receptivity analysis and next-generation sequencing provide insights into ER, but there is a lack of research on these in the Indian population, particularly in patients with RIF. This retrospective cohort study evaluates the effectiveness of Optimal Timing for Endometrial Receptivity Analysis (OpERA)-guided personalized embryo transfer (pET) in Indian patients with a history of RIF. Methodology The study includes 158 female patients with a history of failed embryo transfers who underwent OpERA testing before frozen embryo transfer. Patients were categorized based on the number of previous failed transfers. OpERA outcomes were assessed, and clinical outcomes were compared between groups undergoing preimplantation genetic testing for aneuploidy (PGT-A) with and without OpERA. Endometrial preparation involved hormone replacement therapy, and OpERA testing was performed at the Neuberg Centre for Genomic Medicine using RNA extraction, cDNA conversion, and sequencing. Results OpERA outcomes showed no significant differences in receptive rates among patient groups. Group 3, with three or more failed transfers, exhibited significantly higher biochemical pregnancy rates (BPRs), clinical pregnancy rates (CPRs), and abortion rates (ARs) compared to Groups 1 and 2. OpERA with PGT-A showed significantly higher BPR, implantation rate, CPR, and lower AR compared to OpERA without PGT-A. Conclusions OpERA-guided pET, especially with PGT-A, demonstrated improved pregnancy outcomes, particularly in patients with a history of RIF. The study emphasizes the importance of OpERA in determining optimal transfer timing, moving beyond the traditional reliance on embryo quality alone. OpERA presents promise in predicting pregnancy outcomes for Indian patients with previous IVF failures. The integration of OpERA and PGT-A represents a significant advancement in personalized reproductive medicine, offering new hope for individuals grappling with infertility complexities.

6.
Children (Basel) ; 11(3)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38539402

ABSTRACT

Opsoclonus-myoclonus ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare disorder that presents with myoclonus, ataxia, abnormal eye movements, irritability, and sleep disruptions, often in young children. We report a case of an infant barely 6 months old, with no significant past medical history, who presented to the emergency department with tremors, jerking motions of the head and arms, and rapid eye movements. After an extensive workup, she was found to have a neuroblastoma, which was subsequently surgically removed via thoracotomy. Despite an initial improvement in symptoms post-resection, the patient's symptoms recurred. She was subsequently treated with dexamethasone, intravenous immunoglobulin (IVIG), and rituximab. After treatment, the patient was noted to have mild global developmental delays but was otherwise well. This case report highlights the rare occurrence of OMAS in an infant barely 6 months old at diagnosis. Using the PubMed database, a systematic review was conducted to highlight the clinical presentation, diagnosis, and management of OMAS.

7.
Article in English | MEDLINE | ID: mdl-38502243

ABSTRACT

A multifunctional scaffold protein termed Disabled-2 (Dab2) has recently gained attention in the scientific community and has emerged as a promising candidate in the realm of cancer research. Dab2 protein is involved in a variety of signaling pathways, due to which its significance in the pathogenesis of several carcinomas has drawn considerable attention. Dab2 is essential for controlling the advancement of cancer because it engages in essential signaling pathways such as the Wnt/ß-catenin, epidermal growth factor receptor (EGFR), and transforming growth factor-beta (TGF-ß) pathways. Dab2 can also repress epithelial-mesenchymal transition (EMT) which is involved in tumor progression with metastatic expansion and adds another layer of significance to its possible impact on cancer spread. Furthermore, the role of Dab2 in processes such as cell growth, differentiation, apoptosis, invasion, and metastasis has been explored in certain investigative studies suggesting its significance. The present review examines the role of Dab2 in the pathogenesis of various cancer subtypes including breast cancer, ovarian cancer, gastric cancer, prostate cancer, and bladder urothelial carcinoma and also sheds some light on its potential to act as a therapeutic target and a prognostic marker in the treatment of various carcinomas. By deciphering this protein's diverse signaling, we hope to provide useful insights that may pave the way for novel therapeutic techniques and tailored treatment approaches in cancer management. Preclinical and clinical trial data on the impact of Dab2 regulation in cancer have also been included, allowing us to delineate role of Dab2 in tumor suppressor function, as well as its correlation with disease stage classification and potential therapy options. However, we observed that there is very scarce data in the form of studies on the evaluation of Dab2 role and treatment function in carcinomas, and further research into this matter could prove beneficial in the generation of novel therapeutic agents for patient-centric and tailored therapy, as well as early prognosis of carcinomas.

8.
Res Sq ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38410478

ABSTRACT

Aging is associated with a decline in stem cell functionality and number across the organism. In this study, we aimed to further unravel Muscle Stem Cells (MuSCs) aging by assessing how systemic factors influence MuSC fate decisions through long-term epigenetic landscape remodelling. As aging is intricately linked to a pro-inflammatory shift, we studied the epigenetic effects of inflammatory signals in MuSCs and measured decreased H4K20me1 levels. This loss disrupts MuSC quiescence, largely through epigenetic silencing of Notch target genes. In the setting of inflammatory signals or aging, the lack of Kmt5a and the subsequent absence of de novoH4K20me1 culminate in cell death by ferroptosis. Aged MuSCs manifest abnormal iron metabolism and reduced Gpx4 levels, resulting in the accumulation of intracellular iron, increased reactive oxygen species, genomic instability, and lipid peroxidation. We showed that ferroptosis is the predominant mode of cell death in aged MuSCs, with remarkably high levels of lipid peroxidation; a phenomenon we also observed in aged hematopoietic stem cells. Implementing preventative strategies to inhibit systemic inflammation prevented aged MuSC ferroptosis, preserving their numbers and regenerative capabilities. This intervention significantly enhanced aged muscle regeneration and strength recovery and extended both lifespan and healthspan in mice. This study delineates a previously underappreciated fate trajectory for stem cell aging, and offers meaningful insights into the treatment of age-related disorders.

9.
Redox Biol ; 70: 103047, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38295577

ABSTRACT

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90 % of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca2+]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, total mitochondrial ROS generation was only 56 ± 17 % of that seen with succinate alone (mean ± 95 % confidence intervals). Of this ROS, only 52 ± 20 % was assignable to Cx-I RET. A further 14 ± 7 % could be assigned to complex III, with the remainder (34 ± 11 %) likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion.


Subject(s)
Electron Transport Complex I , Reperfusion Injury , Mice , Animals , Reactive Oxygen Species/metabolism , Electron Transport Complex I/metabolism , Electrons , Electron Transport , Mitochondria, Heart/metabolism , Reperfusion Injury/metabolism , Reperfusion , Succinates
11.
bioRxiv ; 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-38045326

ABSTRACT

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90% of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca2+]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, overall mitochondrial ROS generation was only 56% of that seen with succinate alone, and only 52% of this ROS was assignable to Cx-I RET. The residual non-RET ROS could be partially assigned to complex III (Cx-III) with the remainder likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion.

12.
J Am Acad Dermatol ; 89(5): 1015-1021, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37451624

ABSTRACT

BACKGROUND: Infantile hemangiomas (IHs) of the anogenital region remain poorly characterized. OBJECTIVE: To examine the distribution, ulceration rate, and associated congenital anomalies of anogenital IHs. METHODS: Retrospective study at 8 tertiary referral centers. RESULTS: A total of 435 infants with an IH of the anogenital region were enrolled (of which, 319 [73%] were girls). Congenital anomalies were present in 6.4% (n = 28) of infants with an anogenital IH. Segmental or partial segmental anogenital IHs ulcerated in 72% (n = 99 of 138) of infants, whereas 45% (n = 133 of 297) of focal anogenital IHs experienced ulceration (P < .001). In a multivariable logistic regression analysis, segmental or partial segmental morphology (adjusted odds ratio [aOR], 2.70; 95% CI, 1.60-4.64), mixed type (aOR, 3.44; 95% CI, 2.01-6.07), and perianal (aOR, 3.01; 95% CI, 1.53-6.12) and buttocks location (aOR, 2.08; 95% CI, 1.17-3.76) had increased odds of ulceration. Segmental or partial segmental IHs of the genitalia were confined to distinct anatomic territories and were predominantly distributed unilaterally, with a linear demarcation at the perineal raphe. LIMITATIONS: Possible selection bias, given recruitment at tertiary referral centers. CONCLUSION: This study improves our understanding of high-risk features of anogenital IHs and demonstrates that genital segmental or partial segmental IHs develop within distinct anatomic territories.

13.
Am J Hum Genet ; 110(7): 1034-1045, 2023 07 06.
Article in English | MEDLINE | ID: mdl-37279760

ABSTRACT

Newborn genomic sequencing (NBSeq) to screen for medically important genetic information is of considerable interest but data characterizing the actionability of such findings, and the downstream medical efforts in response to discovery of unanticipated genetic risk variants, are lacking. From a clinical trial of comprehensive exome sequencing in 127 apparently healthy infants and 32 infants in intensive care, we previously identified 17 infants (10.7%) with unanticipated monogenic disease risks (uMDRs). In this analysis, we assessed actionability for each of these uMDRs with a modified ClinGen actionability semiquantitative metric (CASQM) and created radar plots representing degrees of penetrance of the condition, severity of the condition, effectiveness of intervention, and tolerability of intervention. In addition, we followed each of these infants for 3-5 years after disclosure and tracked the medical actions prompted by these findings. All 17 uMDR findings were scored as moderately or highly actionable on the CASQM (mean 9, range: 7-11 on a 0-12 scale) and several distinctive visual patterns emerged on the radar plots. In three infants, uMDRs revealed unsuspected genetic etiologies for existing phenotypes, and in the remaining 14 infants, uMDRs provided risk stratification for future medical surveillance. In 13 infants, uMDRs prompted screening for at-risk family members, three of whom underwent cancer-risk-reducing surgeries. Although assessments of clinical utility and cost-effectiveness will require larger datasets, these findings suggest that large-scale comprehensive sequencing of newborns will reveal numerous actionable uMDRs and precipitate substantial, and in some cases lifesaving, downstream medical care in newborns and their family members.


Subject(s)
Genetic Testing , Genome, Human , Humans , Infant, Newborn , Neonatal Screening , Genomics , Exome Sequencing
14.
JAMA Netw Open ; 6(5): e2312231, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37155167

ABSTRACT

Importance: Newborn genome sequencing (NBSeq) can detect infants at risk for treatable disorders currently undetected by conventional newborn screening. Despite broad stakeholder support for NBSeq, the perspectives of rare disease experts regarding which diseases should be screened have not been ascertained. Objective: To query rare disease experts about their perspectives on NBSeq and which gene-disease pairs they consider appropriate to evaluate in apparently healthy newborns. Design, Setting, and Participants: This survey study, designed between November 2, 2021, and February 11, 2022, assessed experts' perspectives on 6 statements related to NBSeq. Experts were also asked to indicate whether they would recommend including each of 649 gene-disease pairs associated with potentially treatable conditions in NBSeq. The survey was administered between February 11 and September 23, 2022, to 386 experts, including all 144 directors of accredited medical and laboratory genetics training programs in the US. Exposures: Expert perspectives on newborn screening using genome sequencing. Main Outcomes and Measures: The proportion of experts indicating agreement or disagreement with each survey statement and those who selected inclusion of each gene-disease pair were tabulated. Exploratory analyses of responses by gender and age were conducted using t and χ2 tests. Results: Of 386 experts invited, 238 (61.7%) responded (mean [SD] age, 52.6 [12.8] years [range 27-93 years]; 126 [52.9%] women and 112 [47.1%] men). Among the experts who responded, 161 (87.9%) agreed that NBSeq for monogenic treatable disorders should be made available to all newborns; 107 (58.5%) agreed that NBSeq should include genes associated with treatable disorders, even if those conditions were low penetrance; 68 (37.2%) agreed that actionable adult-onset conditions should be sequenced in newborns to facilitate cascade testing in parents, and 51 (27.9%) agreed that NBSeq should include screening for conditions with no established therapies or management guidelines. The following 25 genes were recommended by 85% or more of the experts: OTC, G6PC, SLC37A4, CYP11B1, ARSB, F8, F9, SLC2A1, CYP17A1, RB1, IDS, GUSB, DMD, GLUD1, CYP11A1, GALNS, CPS1, PLPBP, ALDH7A1, SLC26A3, SLC25A15, SMPD1, GATM, SLC7A7, and NAGS. Including these, 42 gene-disease pairs were endorsed by at least 80% of experts, and 432 genes were endorsed by at least 50% of experts. Conclusions and Relevance: In this survey study, rare disease experts broadly supported NBSeq for treatable conditions and demonstrated substantial concordance regarding the inclusion of a specific subset of genes in NBSeq.


Subject(s)
Chondroitinsulfatases , Rare Diseases , Male , Adult , Humans , Infant, Newborn , Female , Middle Aged , Aged , Aged, 80 and over , Rare Diseases/diagnosis , Rare Diseases/genetics , Neonatal Screening , Parents , Amino Acid Transport System y+L , Monosaccharide Transport Proteins , Antiporters
15.
Cureus ; 15(1): e34341, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36865962

ABSTRACT

Vaginal vault prolapse is a painful condition in which the vaginal cuff descends. This report presents a case of a 65-year-old obese and diabetic female who was suffering from a third-degree vault prolapse. Conventionally used non-surgical treatments, such as exercises for the pelvic floor, are not as effective as surgical approaches for the treatment of third-degree vault prolapse. Post-hysterectomy vaginal vault prolapse can be treated safely and effectively with abdominal sacral colpopexy using a permanent mesh. Due to several risk factors, such as grand parity, advancing age, and poor lifestyle mainly involving exercise to strengthen pelvic floor musculature, the vaginal route of surgery was employed, which was found to be effective, and thus the treatment was successful. In conclusion, such individualized as well as unique approaches to such rare cases can produce efficacious results.

16.
Indian J Tuberc ; 70(1): 42-48, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36740317

ABSTRACT

BACKGROUND: Diagnostic modalities for diagnosing Tuberculosis caused by Mycobacterium group of organisms include mainly AFB smear by Ziehl Neelsen carbol fuchsin smear microscopy, GeneXpert (CB NAAT) molecular method, Line probe assay (Molecular method) and AFB culture (Liquid automated systems and solid media) methods. METHODS: This study was initiated to understand and prioritize TB lab diagnosis, with reference to selection of lab diagnostic tests and its order of preference for MTC and NTM/MOTT closely associating it with the TB irradication program initiated by the Government of India. RESULT AND CONCLUSION: The results and discussion bring to light the importance of each test and the purpose of their requisition. When diagnosis is handled half heartedly eradication of TB becomes a challenge. All the efforts including planning, resources in the form of manpower, infrastructure, finances, education, time etc., would be hampered. This challenge is not only for India but the globe. For countries harboring TB, Correct diagnostic request and timely diagnosis and treatment is the key to eradication of tuberculosis.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Rifampin , Sensitivity and Specificity , Tuberculosis/diagnosis , Microscopy , Sputum/microbiology
17.
Eur J Med Genet ; 66(5): 104730, 2023 May.
Article in English | MEDLINE | ID: mdl-36801247

ABSTRACT

Whole exome sequencing is recommended as the first tier test for neurodevelopmental disorders (NDDs) with trio being an ideal option for the detection of de novo variants. Cost constraints have led to adoption of sequential testing i.e. proband-only whole exome followed by targeted testing of parents. The reported diagnostic yield for proband exome approach ranges between 31 and 53%. Typically, these study designs have aptly incorporated targeted parental segregation before concluding a genetic diagnosis to be confirmed. The reported estimates however do not accurately reflect the yield of proband only standalone whole -exome, a question commonly posed to the referring clinician in self pay medical systems like India. To assess the utility of standalone proband exome (without follow up targeted parental testing), we retrospectively evaluated 403 cases of neurodevelopmental disorders referred for proband-only whole exome sequencing at Neuberg Centre for Genomic Medicine (NCGM), Ahmedabad during the period of January 2019 and December 2021. A diagnosis was considered confirmed only upon the detection of Pathogenic/Likely Pathogenic variants in concordance with patient's phenotype as well as established inheritance pattern. Targeted parental/familial segregation analysis was recommended as a follow up test where applicable. The diagnostic yield of the proband-only standalone whole exome was 31.5%. Only 20 families submitted samples for follow up targeted testing, and a genetic diagnosis was confirmed in twelve cases increasing the yield to 34.5%. To understand factors leading to poor uptake of sequential parental testing, we focused on cases where an ultra-rare variant was detected in hitherto described de novo dominant neurodevelopmental disorder. A total of 40 novel variants in genes associated with de novo autosomal dominant disorders could not be reclassified as parental segregation was denied. Semi-structured telephonic interviews were conducted upon informed consent to comprehend reasons for denial. Major factors influencing decision making included lack of definitive cure in the detected disorders; especially when couples not planning further conception and financial constraints to fund further targeted testing. Our study thus depicts the utility and challenges of proband-only exome approach and highlights the need for larger studies to understand factors influencing decision making in sequential testing.


Subject(s)
Neurodevelopmental Disorders , Resource-Limited Settings , Humans , Child , Exome Sequencing , Retrospective Studies , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , Parents
18.
JAMA Dermatol ; 158(11): 1319-1320, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36223112

ABSTRACT

A 3-month-old infant presented with bright red macules, papules, and plaques that appeared at birth and grew in size and number. What is your diagnosis?


Subject(s)
Hemangioma , Skin Neoplasms , Infant , Humans , Hemangioma/diagnosis , Hemangioma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology
19.
Disabil Rehabil Assist Technol ; : 1-8, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35930451

ABSTRACT

PURPOSE: Despite increased usage of telemedicine to deliver treatment during the coronavirus disease 2019 (COVID-19) pandemic, the efficacy of telerehabilitation for spine pain is unknown. This study aimed to investigate the effect of telerehabilitation on pain and disability in patients with spine pain treated during the COVID-19 pandemic and compare the results to in-clinic rehabilitation. MATERIALS & METHODS: In this propensity score-matched analysis, 428 patients with spine pain who underwent telerehabilitation during the 6 months of COVID-19 pandemic lockdown and 428 patients who underwent in-clinic multimodal rehabilitation treatment during the 6-month period prior to lockdown were compared. Propensity score matching was done based on gender, age, pre-treatment pain, and disability. Post-treatment numerical pain rating scale (NPRS), Oswestry or Neck disability index (ODI or NDI), and minimal clinical important difference (MCID) achieved for NPRS and ODI/NDI scores were compared between the 2 groups. RESULTS: Post-treatment, the mean NPRS (mean difference - 1, p < 0.0001) and ODI/NDI (mean difference - 5.8, p < 0.0001) scores, were significantly lower in the telerehabilitation group when compared to control group. Similarly, the percentage of patients who achieved MCID of ≥ 2 for NPRS (mean difference - 6%, p = 0.0007) and MCID of ≥ 10 for ODI/NDI (mean difference - 7.5%, p = 0.005) scores were significantly higher in the telerehabilitation group. CONCLUSIONS: Telerehabilitation achieved significant reduction in pain and disability among patients with spine pain, better than in-clinic rehabilitation. These encouraging results during the COVID-19 pandemic indicate the need to further explore and test the efficacy and wider application of telerehabilitation for treating spine pain.IMPLICATIONS FOR REHABILITATIONTelerehabilitation can help achieve significant reduction in pain and disability among patients with spine pain.These encouraging results indicate the need to further explore a wider application of telerehabilitation for treating patients with spine pain during non-pandemic times.

20.
Turk J Orthod ; 35(2): 150-156, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35788440

ABSTRACT

The aim of this analysis was to evaluate the maxillary incisor intrusion and change in overbite achieved by micro-implants compared to Connecticut intrusion arches among post-pubertal patients with deep bite. Medline, PubMed, Cochrane, and Google scholar were searched for studies falling under the inclusion criteria. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) com- paring maxillary incisor intrusion among post-pubertal deep bite cases treated by mini-implants and Connecticut intrusion arches were to be included. Outcome data were extracted using guidelines published by the Cochrane Collaboration. A systematic review was conducted using Cochrane Program Review Manager, version 5. A random effects model was used to assess the mean difference in the amount of incisor intrusion and overbite correction achieved between the 2 methods. Statistical significance was set at P < .05. Assessment of certainty of evidence was conducted using GRADE analysis. Six trials met the inclusion criteria. Mean differences for incisor intrusion -0.67 [95% CI, 0.97, 0.38] I2 = 31%; P < .00001) and overbite correction -0.51 [95% CI, 0.85, 0.16] I2 = 50%; P = .004) achieved with mini-implants were found to be significantly effective when compared to the Connecticut intrusion arch. Low to mod- erate heterogeneity was noted for incisor intrusion and change in overbite analysis respectively. High certainty of evidence was noted for higher association of mini-implants with incisor intrusion and overbite correction. Our meta-analysis suggests that mini-implants are superior to the Connecticut intrusion arch with respect to the amount of incisor intrusion and overbite correction. Further studies are still needed to confirm the superiority.

SELECTION OF CITATIONS
SEARCH DETAIL
...