Basal expression of RAD51 foci predicts olaparib response in patient-derived ovarian cancer xenografts.

BACKGROUND: The search for biomarkers to evaluate ovarian cancer (OC) homologous recombination (HR) function and predict the response to therapy is an urgent clinical need to improve the selection of patients who could benefit from platinum- and olaparib (poly-ADP ribose polymerase inhibitors, PARPi)-based therapies. METHODS: We used a large collection of OC patient-derived xenografts (PDXs) (n = 47) and evaluated their HR status based on BRCA1/2 mutations, BRCA1 promoter methylation and the HRDetect score. RAD51 foci were quantified in formalin-fixed, paraffin-embedded untreated tumour specimens by immunofluorescence and the messenger RNA expression of 21 DNA repair genes by real-time PCR. RESULTS: Tumour HR deficiency predicted both platinum and olaparib responses. The basal level of RAD51 foci evaluated in geminin-positive/replicating cells strongly inversely correlated with olaparib response (p = 0.011); in particular, the lower the foci score, the greater the sensitivity to olaparib, while low RAD51 foci score seems to associate with platinum activity. CONCLUSIONS: The basal RAD51 foci score is a candidate predictive biomarker of olaparib response in OC patients as it can be easily translatable in a clinical setting. Moreover, the findings corroborate the importance of OC-PDXs as a reliable tool to identify and validate biomarkers of response to therapy.

Routine Maternal Vaccine Uptake during the COVID-19 Pandemic.

OBJECTIVE: This study examines the impact of the coronavirus disease 2019 (COVID-19) pandemic on influenza and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine uptake in a pregnant, low-income population. STUDY DESIGN: This retrospective cohort study included women initiating prenatal care before (May-November 2019) or during the COVID-19 pandemic (May-November 2020) at two large Medicaid clinics. All patients entered prenatal care before 20 weeks and delivered full-term. Medical records were reviewed for vaccine uptake and demographic data. Multivariate logistic regression analysis was used to compare vaccination rates prior to and during the COVID-19 pandemic. Additional analysis was performed to identify association of demographic factors with vaccine uptake. IRB approval was obtained for this study. RESULTS: A total of 939 patients met inclusion criteria, with 462 initiating care prior to and 477 initiating care during the COVID-19 pandemic. Influenza vaccination uptake was 78% (362/462) in the prepandemic group, significantly decreasing to 61% (291/477) in the pandemic group (p <0.01, odds ratio [OR] = 0.38, confidence interval [CI]: 0.26-0.53). Tdap vaccination uptake was 85% (392/462) in the prepandemic group, significantly decreasing to 76% (361/477) in the pandemic group (p <0.01, OR = 0.56, CI: 0.40-0.79). The decrease in influenza vaccine uptake was most significant in non-Hispanic Black patients, decreasing from 64% (73/114) in the prepandemic group to 35% (35/101) in the pandemic group (p <0.01, OR = 0.30, CI: 0.17-0.52), while there was no significant difference in age or parity in relation to vaccination status. CONCLUSION: Routine vaccination uptake significantly decreased during the COVID-19 pandemic in a low-income population of pregnant women, with decrease more pronounced on influenza vaccine than on Tdap vaccine uptake, especially in non-Hispanic Black patients. KEY POINTS: · Influenza and Tdap vaccination uptake during pregnancy has decreased during the COVID-19 pandemic.. · Influenza vaccine uptake decreased more than Tdap in pregnancy during the COVID-19 pandemic.. · The greatest decrease was seen in influenza vaccine uptake in non-Hispanic Black patients..

Evaluation of the impact of early childhood caries, traumatic dental injury, and malocclusion on oral health-Related quality of life for Turkish preschool children and families.

AIM: The aim of this study was to assess the impact of the presence of early childhood caries (ECC), traumatic dental injury (TDI), and malocclusion, as well as severe conditions, on the oral health-related quality of life (OHRQoL) of preschool children and families. MATERIALS AND METHODS: A cross-sectional survey was conducted in children aged 1 to 6 years old, who attended to the Department of Paediatric Dentistry, Gazi University. The questionnaires were adapted to Turkish, and OHRQoL was measured using the Turkish version of Early Childhood Oral Health Impact Scale (T-ECOHIS). Children were classified into four main groups, two subgroups in each group based on their severity conditions-Group 1: ECC group; Group 2: TDI group; Group 3: Malocclusion group; Group 4: Control group. Parents answered the questions about sociodemographic conditions and T-ECOHIS. The Kolmogorov-Smirnov test was used for non-normal distribution and Kruskal-Wallis and Mann-Whitney tests were used to compare T-ECOHIS score regarding ECC, TDI, and malocclusion. RESULTS: Both simple and severe conditions of TDI showed a negative impact on the family and child based on T-ECOHIS scores (P < 0.05). The severe condition of ECC and malocclusion showed significantly negative impact on family (P > 0.05) but not on child (P > 0.0.5). CONCLUSION: The presence of ECC, TDI, and malocclusion has a negative effect on OHRQoL of Turkish preschool children and specially their families. So, public health programs should be carried out about oral health for raising parents' and children's awareness and increasing OHRQoL.

Comparison of three different ketofol proportions in children undergoing dental treatment.

AIM AND BACKGROUND: Sedation is gaining popularity among dental procedures in children. Ketamine and propofol mixture, known as ketofol, is one of the promising choices in sedation protocols; however, there is no consensus on the exact ratio of ketamine plus propofol especially in dental practice. The aim of present study was to compare perioperative side effect profiles, recovery profiles, and satisfaction rates of both parents' and dentists' following three different ratio of ketofol mixtures in children undergoing dental treatment. Materials and. METHODS: Three study groups each containing 30 children scheduled for dental treatment were created. Following anesthesia induction with 5% sevoflurane, 50% nitrous oxide mixture in 50% oxygen, 1 mg/kg bolus ketofol dose was administered. Patients in Group 1 received ketofol as a 1:1 mixture, patients in Group 2 received 1:2 ketofol while in Group 3; 1:4 ketofol was administered at a constant dose of 100 µg/kg/min. Additional doses of the ketofol solution at the same concentration with infused solutions in groups (0.5 mg/kg from either 1:1, 1:2, or 1:4 proportions) were administered if required. Perioperative vital signs, side effects, postoperative side effects, recovery durations, parents' and dentists' satisfaction levels were compared between groups. RESULTS: There were no significant differences between groups in terms of perioperative vital signs and side effects. Depth of sedation, dentists' satisfaction levels and postoperative side effects -myoclonus, hypersalivation and tachycardia were significantly higher in Group 1. Parents' satisfaction was highest in Group 3, however, necessity of additional doses and dissatisfaction of dentists' were found highest in this group. Mean duration of recovery recorded in Group 3 was shortest compared with other groups. CONCLUSION: Decreased ketamine doses in ketofol mixture was related with decreased side effect profile, high parents' satisfaction with fast recovery, however, dentists' satisfaction was lower. In this context, results of present study indicated that ketofol mixture of 1:2 ratio was more reliable choice than others when all investigated parameters evaluated simultaneously.

The influence of orthosis options on walking parameters in spinal cord-injured patients: a literature review.

OBJECTIVE: Orthoses for various joints sections are considered to greatly influence the gait function and energy expenditure in spinal cord-injured (SCI) patients. The aim of this review was to determine the influence of orthoses characteristics and options on the improvement of walking in patients with SCI. METHODS: A search was performed using the Population Intervention Comparison Outcome (PICO) method, based on selected keywords; studies were identified electronically in the Science Direct, Google Scholar, Scopus, Web of Knowledge and PubMed databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used to report the results. Assessment of the quality of all articles was performed based on the Physiotherapy Evidence Database (PEDro scale). RESULTS: Twelve studies evaluated the effects of different hip joint options on walking parameters and energy expenditure. Five studies investigated the role of knee joint options on gait parameters and compensatory trunk motion. Only five studies analyzed modified ankle joints on gait parameters in SCI patients. Nine studies analyzed gait parameters in SCI patients as powered orthoses and exoskeleton. These studies had a low level of evidence according to the PEDro score (2/10). CONCLUSION: The various joint types of orthoses appear to be critical in the improvement of walking in patients with SCI. In particular, 'user friendly' orthoses that support the related structure such as the hip joint with a reciprocating mechanism, activated knee joint and movable ankle joint with dorsiflexion assist enable SCI patients to optimize their walking pattern when wearing an orthoses system.

The influence of orthotic gait training with an isocentric reciprocating gait orthosis on the walking ability of paraplegic patients: a pilot study.

OBJECTIVES: The aim of this study was to evaluate the influence of walking with an isocentric reciprocating gait orthosis (IRGO) by spinal cord injury (SCI) patients on walking speed, distance walked and energy consumption whilst participating in a 12-week gait re-training program. METHODS: Six people with motor complete SCI (mean age 29 years, weight 63 kg and height 160 cm with injury levels ranging from T8 to T12) participated in this study. Gait evaluation was performed at baseline and after 4, 8 and 12 weeks. Walking speed and heart rate were measured to calculate the resulting physiological cost index (PCI). RESULTS: Reductions in energy consumption were observed after 4, 8 and 12 weeks compared with baseline but were not significant. However, walking distance increased significantly (P=0.010, P=0.003 and P=0.005, respectively) and also did so during the 8-12-week period (P=0.013). Walking speed also improved, but not significantly. CONCLUSION: Intensive gait training with the IRGO improved walking speed and the distance walked by paraplegics, as well as reducing the PCI of walking, as compared with baseline during the whole 12-week period. This indicates that further improvements in these parameters may be expected when utilizing gait training longer than 8 weeks.

The influence of new reciprocating link medial linkage orthosis on walking and independence in a spinal cord injury patient.

OBJECTIVES: The purpose of this paper is to describe the development and evaluation of a new medial linkage reciprocating gait orthosis (MLRGO) that incorporates a reciprocal mechanism and is sensitive to pelvic motion to potentially assist paraplegic patients to walk and provide functional independence. CASE DESCRIPTION AND METHODS: The new orthosis was constructed and tested by a 20-year-old female paraplegic subject with transverse myelitis at T10 level, who was 4 years post injury and had also been an isocentric reciprocating gait orthosis (IRGO) user for 2 years. She received gait training for 12 weeks before undertaking gait analysis, and also completed a questionnaire that was designed to assess the perceived functionality of the new MLRGO when compared with an IRGO. RESULTS: The results demonstrated improvements in gait velocity, step length and cadence, and also improvement in functional independence with the new orthosis compared with an IRGO. CONCLUSION: The results demonstrated that this new MLRGO could be used for paraplegic patients who would like an improvement in functional independence and ambulation.

The efficiency of orthotic interventions on energy consumption in paraplegic patients: a literature review.

Study design:This is a systematic literature review.Objectives:Different types of orthoses have been developed to enable and facilitate ambulation in individuals with paraplegia. However, their effect on energy consumption while ambulating is not clear. The objective of this review was to compare the energy expenditure required to walk with these devices.Methods:Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, and based on selected keywords and their composition according to the Population Intervention Comparison Outcome (PICO) method, a search was performed in Science Direct, Google Scholar, Scopus, Web of Knowledge and PubMed databases. The searches were restricted to papers published in the English language and were conducted during February 2014; the last access to the database was on 25 February 2014. A total of 24 articles were chosen for final evaluation.Results:Hybrid orthoses reduce energy consumption compared with mechanical orthoses when used for walking by paraplegic patients. The isocentric reciprocating gait orthosis has been shown to be more effective than other reciprocating orthoses in reducing energy consumption. Energy consumption when walking with powered orthoses (PO) and hybrid orthoses was also reduced compared with when walking with conventional orthoses.Conclusions:The hybrid orthoses and PO could be effective alternatives in rehabilitation for spinal cord injury patients to help improve the energy consumption.Spinal Cord advance online publication, 20 January 2015; doi:10.1038/sc.2014.227.

Design and analysis of a new medial reciprocal linkage using a lower limb paralysis simulator.

STUDY DESIGN: A feasibility study on the effect of a new reciprocating orthosis on specific gait parameters for use by people with spinal cord injury. OBJECTIVES: The aim of this study was to design and develop a new medial linkage orthosis (MLO) mechanism incorporating a reciprocating motion and to determine its efficacy in improving specific spatiotemporal, kinematic and kinetic parameters while ambulating when worn by healthy subjects. This was achieved via the use of a lower limb paralysis simulator (LLPS). METHODS: A reciprocating joint with a remote center of motion was designed for use as an MLO. A prototype was fabricated and incorporated into an orthosis and equipped with a saddle to make the reciprocating motion possible. The efficacy of the orthosis was evaluated on four able-bodied healthy subjects who were trained to walk with the MLO attached to the LLPS. RESULTS: Mean walking speed, stride length, stride time and cadence was 0.09±0.007 m s(-1), 0.42±0.01 m, 4.89±0.45 s and 29.54±4.32 steps min(-1), respectively, when healthy subjects walked with the new orthosis. The mean hip joint torque produced was 0.36±0.13 Nm. CONCLUSION: In this study a new MLO was designed and fabricated that provided a reciprocating mechanism using a four-bar mechanism to set the virtual axis of the mechanism in a more proximal position than hinge-type joints. Further investigation is currently underway to assess its effect on gait parameters and energy expenditure in paraplegic patients.

Are behaviour risk factors for traumatic dental injuries in childhood different between males and females?

AIM: Examination of the risk factors for childhood traumatic dental injuries for male and female patients have been elusive. The present study aimed to examine whether males and females are differentially vulnerable to Traumatic Dental Injuries in relation to emotion regulation, attention deficiency hyperactive disorder symptomatology and behaviour problems. MATERIALS AND METHODS: An institutional ethical review board approved the case-control study carried out at the Gazi University, Faculty of Dentistry, Turkey. A total of 80 patients with traumatic dental injuries and 80 patients with other dental problems participated in the study. Patients' parents filled in two scales: Conners' Rating Scales-Revised Attention Deficiency Hyperactive Disorder-Index, Oppositional Behavior, Hyperactivity, Anxious-Shy, Social Problems, Inattentive and Hyperactive-Impulsive subscales; and Emotion Regulation Checklist, with two subscales of Emotional Lability and Emotion Regulation. Multiple logistic regression analyses were performed separately for male and female patients. RESULTS: Oppositional behaviour, hyperactivity and social problems were found to be risk factors for male patients. Being anxious/shy was the protective factor for both males and females. Classification accuracy for males and females were calculated to be 79.2% and 85.2% respectively. CONCLUSION: Several risk factors for childhood traumatic dental injuries were found to differ for male and female patients.

The reasons for extractions of primary teeth in Turkish children.

AIM: The aim of this study was to determine the current reasons for primary teeth extractions in Turkish children and their relative importance. STUDY DESIGN: retrospective evaluation of patients by analysing dental records of children aged 2-13 years, receiving treatment in different regions in Turkey over a period of five years (2007-2012). Patient's age, gender, any significant medical finding, type of tooth extracted and the reason for the extraction were the parameters evaluated. RESULTS: It resulted that 2,508 primary teeth belonging to 1,755 children aged of 2-13 years were extracted. Extraction due to caries (57,4%) was found to be the most common reason. STATISTICS: Chi-square tests were performed for statistical analysis. Although no differences in the types of teeth extracted were observed between genders, striking differences were noted in the different age groups. CONCLUSION: From this study it can be concluded that caries and subsequent pulpal pathology are the most common reasons for extraction of primary teeth in Turkey. Primary molars were the most common tooth type extracted. Preventive programmes for preschool children should be given importance.

Comparison of gait between healthy participants and persons with spinal cord injury when using a powered gait orthosis-a pilot study.

OBJECTIVES: The aim of this study was to evaluate the effect of a powered gait orthosis (PGO) on the temporal-spatial parameters and kinematics of walking in both healthy participants and persons with spinal cord injury (SCI) using three-dimensional motion analysis to facilitate further development of such devices. METHODS: Kinematics and temporal spatial data were obtained from three healthy participants and four persons with SCI who walked using the same design of PGO. RESULTS: Walking speed was reduced by 28% and step length by 29% in healthy individuals when walking with PGO compared with normal walking and that recorded for persons with SCI was approximately one-third that of normal walking. There were significant differences in hip and knee joint ranges of motion in comparison between walking with PGO in healthy participants and walking with PGO in persons with SCI. CONCLUSION: Walking with a PGO by healthy participants significantly reduced critical gait parameters, and further development work is needed to produce a more effective device to match closely the gait parameters of normal walking by healthy participants. Significant differences between normal walking and that evidenced with the PGO by both healthy participants and persons with SCI were detected.

Utilizing Complexity Leadership Theory to Promote Faculty Mentorship and Resident Leadership.

OBJECTIVE: To create and evaluate a structured combined faculty mentorship/resident leadership program based on complexity leadership theory. DESIGN: In 2021, a logic model was used to create a 5 part bi-monthly resident leadership series utilizing administrative, adaptive, and enabling components of complexity leadership theory. Each of the 5 sessions had a nationally prominent senior faculty member mentor 3 junior faculty in creation of an interactive workshop that was delivered to resident physicians during scheduled didactics. Validated surveys were used to assess faculty post-mentorship experience and resident self-perception of leadership skills pre-and post-series. Descriptive statistics and 2-way ANOVA were performed; text comments underwent content analysis. SETTING: A large academic OB/GYN department at Baylor College of Medicine in Houston, Texas. PARTICIPANTS: Five faculty mentors, 15 junior faculty, and 48 residents participated in this program. All faculty mentors (5/5) and 87% (13/15) of mentees completed the post-mentorship survey. Resident response rate was 60% (29/48) pre-series and 63% (30/48) post-series. RESULTS: Both mentors and mentees rated the experience favorably (4.62 versus 5.29, p = 0.51). In open-ended comments, enabling components of mentorship process, such as approachability and expertise of the mentors, were most often noted as positive. Both mentees and mentors suggested administrative changes to the experience, such as longitudinal relationships between mentors and mentees. The mean score on the resident leadership questionnaire improved from 3.82 to 3.96 (5-point Likert scale, p = 0.30) with self-reported leadership skills improving in 8/9 domains, although none reaching statistical significance. Open-ended comments revealed that residents also most desired administrative changes in the leadership series, such as increased leadership opportunities and more interactive workshops. CONCLUSIONS: A structured combined faculty mentorship/resident leadership program formed utilizing complexity leadership theory was positively received. Participants most liked the enabling components of the series, with requested administrative changes in the future.

Implementation and Evaluation of a Comprehensive Resident Wellness Curriculum During the COVID-19 Pandemic.

OBJECTIVE: To evaluate the effectiveness of resident-led and faculty-led initiatives for physician wellness after implementation of a resident wellness program. DESIGN: We initiated a wellness curriculum with both resident and faculty-led components in a large academic OB/GYN residency program in October 2020. The curriculum was created and evaluated using the Logic model. Residents were surveyed pre and 8 months postintervention with the Maslach Burnout Inventory (MBI) and the Physician Well-Being Index (PWBI), with activity-related questions added to the second survey. Descriptive statistics, Mann-Whitney test, Chi-square test, and theme analysis were performed as appropriate. SETTING: A large academic OB/GYN residency at Baylor College of Medicine in Houston, Texas PARTICIPANTS: All residents (n = 48) were invited to take part in the surveys. Response rate was 31/48 (65%) pre and 28/48 (58%) postintervention. RESULTS: Residents scored moderate for emotional exhaustion and depersonalization and high for personal accomplishment on both pre and post-MBI surveys. All indices of the PWBI improved over time; however, no significant differences were found in pre and postmeasures. Resident-led activities, which were alternated between individualized time off and group resident socialization, were rated significantly higher than faculty-led activities; 93% (52/56) of respondents rated resident-led activities in their top 2 most helpful initiatives compared to 7% (4/56) who rated faculty-led activities in their top 2 most helpful (p < 0.01) initiatives. Open-ended comments revealed that continued focus on wellness, attention to personal health, and systematic change were the most important ways to improve resident wellness. CONCLUSION: Decreases in burnout were not achieved over an 8-month period with program-level resident-led and faculty-led initiatives. Providing scheduled time for residents to use at their discretion and the continuation of events that encourage socialization are tools that are highest rated by residents to facilitate wellness.

Resident-as-Teacher: Can It Be Done With an E-Learning Module?

Background Resident-as-teacher initiatives are traditionally specialty-specific and performed in-person, limiting ability to disseminate essential teaching skills to all residents. Objective The aim of this study was to develop, implement, and evaluate a resident-as-teacher interactive e-learning module on growth mindset and coaching. Methods The module was designed and implemented between August 2022 and March 2023. It was distributed to postgraduate year (PGY) 1 residents in all specialties at a large academic institution. Completion rates, Likert ratings, and answers to 2 open-ended questions were used for assessment. Descriptive statistics and 1-way analysis of variance with Sîdák correction for multiple comparisons were performed on Likert ratings. Responses to open-ended questions were evaluated using content analysis. Results The module was completed by all 277 PGY-1 residents (100%), with the evaluation completed by 276 of 277 (99.6%) residents. Mean rating of the module's relevance to the role of resident teacher was 4.06±0.90 (5-point Likert scale), with general surgery residents rating the module less favorably compared to all specialties (3.28±1.06; P<.01; 95% CI 0.26-1.30). Open-ended comments revealed that residents most liked the delivery of relevant teaching strategies and the interactive design of the module. The most common area for suggested improvement was the addition of content such as teaching in challenging situations. Time needed for design, implementation, and evaluation was 80 hours total. Conclusions An e-learning module offers an interactive platform for teaching skills and was found to be an acceptable method of instruction for residents.

The physiological cost index of walking with mechanical and powered gait orthosis in patients with spinal cord injury.

OBJECTIVES: Mechanical orthoses, such as the hip knee ankle foot orthosis (HKAFO) and the isocentric reciprocating gait orthosis (IRGO), are both used for walking in spinal cord injury (SCI) patients. The aim of this study was to analyze the energy expenditure during walking with these orthoses compared with a powered gait orthosis (PGO) in patients with SCI. METHODS: Five patients with SCI who were experienced users of HKAFOs participated in this study. Subjects were also fitted with an IRGO and PGO and underwent a specific gait training program. Patients walked along a flat walkway using the three types of orthosis at their self-selected walking speed. A stop watch and a polar heart rate monitor were used to measure the speed of walking and heart rate. RESULTS: Walking speed, the distance walked and the physiological cost index (PCI) all improved with both the new PGO and the IRGO as compared with the HKAFO. CONCLUSIONS: A PGO can improve walking speed and the distance walked and reduce the PCI of walking as compared with mechanical orthoses, probably due to the activated movements of the lower limb joints.

The influence of ankle joint mobility when using an orthosis on stability in patients with spinal cord injury: a pilot study.

OBJECTIVES: Perceived risk of falling is an important factor for people with spinal cord injury (SCI). This study investigated the influence of ankle joint motion on postural stability and walking in people with SCI when using an orthosis. METHODS: Volunteer subjects with SCI (n=5) participated in this study. Each subject was fitted with an advanced reciprocating gait orthosis (ARGO) equipped with either solid or dorsiflexion-assist type ankle-foot orthosis (AFOs) and walked at their self-selected speed along a flat walkway to enable the comparison of walking speed, cadence and endurance. A force plate system and a modified Falls Efficacy Scale (MFES) were utilized to measure postural sway and the perceived fear of falling, respectively. RESULTS: There were significant differences in the mean MFES scores between two types of orthosis (P=0.023). When using two crutches, there was no significant difference in static standing postural sway in the medio-lateral (M/L) direction (P=0.799), but significant difference in the antero-posterior (A/P) direction (P=0.014). However, during single crutch support, there was a significant difference in both M/L (P=0.019) and A/P (P=0.022) directions. Walking speed (7%) and endurance (5%) significantly increased when using the ARGO with dorsi flexion assisted AFOs. There was no significant deference between two types of orthoses in cadence (P=0.54). CONCLUSIONS: Using an ARGO with dorsiflexion-assisted AFOs increased the fear of falling, but improved static postural stability and increased walking speed and endurance, and should therefore be considered as an effective orthosis during the rehabilitation of people with SCI.

Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase.

Telomeric DNA of mammalian chromosomes consists of several kilobase-pairs of tandemly repeated sequences with a terminal 3' overhang in single-stranded form. Maintaining the integrity of these repeats is essential for cell survival; telomere attrition is associated with chromosome instability and cell senescence, whereas stabilization of telomere length correlates with the immortalization of somatic cells. Telomere elongation is carried out by telomerase, an RNA-dependent DNA polymerase which adds single-stranded TAGGGT repeats to the 3' ends of chromosomes. While proteins that associate with single-stranded telomeric repeats can influence tract lengths in yeast, equivalent factors have not yet been identified in vertebrates. Here, it is shown that the heterogeneous nuclear ribonucleoprotein A1 participates in telomere biogenesis. A mouse cell line deficient in A1 expression harbours telomeres that are shorter than those of a related cell line expressing normal levels of A1. Restoring A1 expression in A1-deficient cells increases telomere length. Telomere elongation is also observed upon introduction of exogenous UP1, the amino-terminal fragment of A1. While both A1 and UP1 bind to vertebrate single-stranded telomeric repeats directly and with specificity in vitro, only UP1 can recover telomerase activity from a cell lysate. These findings establish A1/UP1 as the first single-stranded DNA binding protein involved in mammalian telomere biogenesis and suggest possible mechanisms by which UP1 may modulate telomere length.

Small cell lung cancer with SYN2::PPARG fusion.

INTRODUCTION: Small cell lung cancer (SCLC) accounts for 15% of lung cancers worldwide. It is an aggressive tumor that is typically diagnosed at an advanced stage. Treatment involves chemo-immunotherapy and/or radiotherapy. Identifying druggable targets activated by specific genetic alterations represents a significant challenge in improving patient outcomes. METHODS: We conducted a retrospective examination of molecular findings in lung cancer patients' records from 2021 to 2022. We discovered a unique case of SCLC harboring the SYN2-PPARG fusion. Histopathological analysis confirmed the diagnosis of SCLC. CASE REPORT: A 60-year-old woman, a heavy smoker, came to our attention due to a persistent cough with slight hemoptysis. Imaging, including axial contrast-enhanced computed tomography, revealed an advanced disease with extra-thoracic spread. Tumor histology showed a sheet-like proliferation of small-sized cells with a neuroendocrine phenotype and a high proliferation tumor cell fraction. Molecular genetic analysis using NGS approach revealed a fusion involving the SYN2 and PPARG genes. CONCLUSION: The SYN2-PPARG fusion has recently been documented in sinonasal adenocarcinoma and has been reported in only a single SCLC case previously. Highlighting the molecular heterogeneity within this aggressive form of lung cancer could potentially aid in the selection of specific therapies.