Female sex and overweight are associated with a lower quality of life in patients with myasthenia gravis: a single center cohort study.

BACKGROUND: Myasthenia gravis (MG) affects individuals as a chronic autoimmune disease for many years. Commonly, chronic diseases significantly reduce the patients' quality of life. Aiming to improve the future quality of life in MG, this study assessed the factors impacting quality of life. As gender-specific medicine is becoming increasingly important, this study also focused on understanding gender differences in the outcome of MG. METHODS: The study is a combined monocentric, retrospective and prospective database analysis of patient records based on 2,370 presentations of 165 patients with clinically, serologically and/or electrophysiologically confirmed MG over an observation period of up to 47 years. The data collection included the following parameters: antibody status, disease severity, age, medication use, gender, and disease duration. In addition, a prospective survey was conducted on the quality of life using the Myasthenia gravis-specific 15-item Quality of Life scale (MG-QoL15) and on the activities of daily living using the MG-specific Activities of Daily Living scale (MG-ADL). RESULTS: Of the 165 patients, 85 were male (51.5%) and 80 were female (48.5%). The remaining baseline characteristics (e.g. age and antibody status) were consistent with other myasthenia gravis cohorts. A high body mass index (BMI) (p = 0.005) and a high disease severity (p < 0.001) were significantly associated with lower disease-specific quality of life. Additionally, the quality of life in women with MG was significantly reduced compared to male patients (19.7 vs. 13.0 points in the MG-QoL15, p = 0.024). Gender differences were also observable in terms of the period between initial manifestation and initial diagnosis and women were significantly more impaired in their activities of daily living (MG-ADL) than men (4.8 vs. 3.0 points, p = 0.032). CONCLUSION: Women with MG had significantly poorer disease specific quality of life compared to men as well as patients with a higher BMI. In order to improve the quality of life, gender-specific medicine and further investigation regarding a modification of the quality of life by lowering the BMI are essential and necessary. TRIAL REGISTRATION: Study approval by the Ethics Committee of the University Medical Center Göttingen was granted (number 6/5/18).

Comparison between cone-beam breast-CT and full-field digital mammography for microcalcification detection depending on breast density.

The purpose of this study was to evaluate the impact of breast density on the diagnostic performance of cone-beam breast-CT (CBBCT) in comparison to full-field digital mammography (FFDM) for the detection of microcalcifications. This retrospective IRB-approved study was conducted between December 2015 and March 2017 and enrolled 171 women with Breast Imaging Reporting and Data System category 4 or 5 lesions on FFDM and additional CBBCT; 56 of which were ineligible. The inclusion was restricted to 83 women (90 breasts, 90 lesions) with microcalcifications. All lesions underwent histology or were monitored by FFDM and a clinical examination at least 2 years after enrollment. Two breast radiologists independently read each data set twice. Sensitivity, specificity and area under the curve were compared between the modalities. Thirty-two breasts (35.5%) were grouped as non-dense breasts (American College of Radiology types a/b) and 58 breasts (64.5%) as dense breasts (American College of Radiology types c/d). Histopathological assessment was performed in 61 of 90 breast lesions (32 malignant, 1 high-risk and 28 benign). Area under the curve was larger for FFDM than for CBBCT (P = .085). The sensitivity was significantly higher for FFDM compared to CBBCT (P = .009). The specificity showed no significant differences comparing FFDM (both readers: 0.62) versus CBBCT (reader 1: 0.76, reader 2: 0.60; P = .192). Inter-observer-reliability on BI-RADS readings was almost perfect for FFDM and moderate for CBBCT (κ = 0.84, κ = 0.54, respectively). Intra-observer agreement was substantial to almost perfect for both methods and readers. Compared with FFDM, CBBCT demonstrated non-comparable results for microcalcification detection in dense and non-dense breasts.

Comparative evaluation of clinical and cerebrospinal fluid biomarker characteristics in rapidly and non-rapidly progressive Alzheimer's disease.

BACKGROUND: Rapidly progressive forms of Alzheimer's disease (rpAD) are increasingly recognized and may have a prevalence of up to 30% of patients among all patients with Alzheimer's disease (AD). However, insights about risk factors, underlying pathophysiological processes, and clinical characteristics of rpAD remain controversial. This study aimed to gain a comprehensive picture of rpAD and new insights into the clinical manifestation to enable a better interpretation of disease courses in clinical practice as well as in future clinical studies. METHODS: Patients (n = 228) from a prospective observational study on AD were selected and categorized into rpAD (n = 67) and non-rpAD (n = 161) disease groups. Patients were recruited through the German Creutzfeldt-Jakob disease surveillance center and the memory outpatient clinic of the Göttingen University Medical Center, representing diverse phenotypes of the AD population. Biomarkers and clinical presentation were assessed using standardized protocols. A drop of ≥ MMSE 6 points within 12 months defined rapid progressors. RESULTS: Lower CSF Amyloid beta 1-42 concentrations (p = 0.048), lower Amyloid beta 42/40 ratio (p = 0.038), and higher Tau/Amyloid-beta 1-42 ratio, as well as pTau/Amyloid-beta 1-42 ratio (each p = 0.004) were associated with rpAD. Analyzes in a subset of the cohort (rpAD: n = 12; non-rpAD: n = 31) showed higher CSF NfL levels in rpAD (p = 0.024). Clinically, rpAD showed earlier impairment of functional abilities (p < 0.001) and higher scores on the Unified Parkinson's Disease Rating Scale III (p < 0.001), indicating pronounced extrapyramidal motor symptoms. Furthermore, cognitive profiles (adjusted for overall cognitive performance) indicated marked deficits in semantic (p = 0.008) and phonematic (0.023) verbal fluency tests as well as word list learning (p = 0.007) in rpAD compared to non-rpAD. The distribution of APOE genotypes did not differ significantly between groups. CONCLUSIONS: Our results suggest that rpAD is associated with distinct cognitive profiles, earlier occurrence of non-cognitive symptoms, extrapyramidal motoric disturbance, and lower Amyloid-beta 1-42 concentrations in the CSF. The findings may help to characterize a distinct phenotype of rpAD and estimate prognosis based on clinical characteristics and biomarker results. However, an important future goal should be a unified definition for rpAD to enable targeted study designs and better comparability of the results.

Benefit of intravitreal injections in patients with sub-threshold baseline visual acuity: a retrospective single-centre study.

PURPOSE: To investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then. METHODS: In this retrospective study, data from patients with a logMAR BCVA ≤ 1.3 and 24 months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO). RESULTS: The data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24 months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6 months and remained stable within 24 months. Patients received a median of 5 and 10 injections within 6 and 24 months, respectively. Median foveal retinal thickness was 594.5 µm at baseline and dropped to 244.5 µm, 235.5 µm, 183 µm, and 180 µm during the four consecutive time intervals. CONCLUSION: Patients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2 years irrespective of the underlying macular disease. Those patients should not be excluded from therapy.

Central retinal artery occlusion - detection score.

Purpose: To investigate the sensitivity and specificity of central retinal artery occlusion (CRAO)-Detection Score in diagnosing CRAO via questionnaire and without fundoscopy. Methods: This prospective study enrolled 176 emergency patients suffering from acute visual loss, of whom 38 were suffering from CRAO. Before conducting any examination, we administered our questionnaire containing six questions, followed by a thorough ophthalmologic examination to make the diagnosis. Statistical analysis involved a LASSO penalised multivariate logistic regression model. Results: Our receiver operating characteristic (ROC) analysis based on a LASSO penalised multivariate logistic regression model showed an area under the curve (AUC) of 0.9 - three out of six questions were selected by LASSO. Interestingly, the unweighted ROC analysis of only two questions (Short CRAO-Detection Score) yielded similar results with an AUC of 0.88. The short CRAO-Detection Score of 2 yielded 14% (4/28) false positive patients. Conclusion: This prospective study demonstrates that a high percentage of CRAO patients are detectable with a questionnaire. The CRAO-Detection Score might be used to triage patients suffering acute visual loss, which is important as intravenous fibrinolysis seem to be time-dependent to be effective.

Left-sided excess in the laterality of cutaneous melanocytic nevi and melanomas.

BACKGROUND AND OBJECTIVES: Asymmetrical distribution of melanomas in favor of the left body half has been repeatedly described. PATIENTS AND METHODS: In a prospective cross-sectional study, we investigated the distribution of melanocytic nevi between the left and right halves of the body in 702 patients. In 2,004 consecutive cases with melanomas, we retrospectively determined left to right (L/R) ratios of primary melanomas, lymph node metastases, and melanocytic nevi in sentinel lymph nodes (SN). RESULTS: The L/R ratios for cutaneous nevi and melanomas were 1.23 (95 % confidence interval [CI] 1.12-1.36) and 1.6 (95 % CI 1.37-1.88), respectively. In both cutaneous nevi and melanomas, the left-sided excess was mainly found in intermittently light-exposed skin. Of the nevus patients, 92.4 % were right-handed. Breslow thickness and rates of ulceration did not differ significantly between the two body halves. CONCLUSIONS: Melanocytic nevi and melanomas are more frequently found on the left body half. We assume asymmetric solar radiation as the causative factor. The vast majority of right-handed people might unconsciously align their posture during outdoor activities so that the light falls in from the left. This avoids shadow cast by the dominant arm, shoulder, or head.

Linksüberhang in der Verteilung von melanozytären Nävi und Melanomen.

HINTERGRUND UND ZIELE: Eine asymmetrische Verteilung von Melanomen zugunsten der linken Körperhälfte wurde wiederholt beschrieben. PATIENTEN UND METHODIK: In einer prospektiven Querschnittstudie untersuchten wir bei 702 Patienten einer dermatologischen Klinik die Verteilung melanozytärer Nävi zwischen der linken und der rechten Körperhälfte. Außerdem bestimmten wir retrospektiv das Verhältnis von links zu rechts (L/R) von primären Melanomen, Lymphknotenmetastasen und Nävi in Sentinel-Lymphknoten (SN) bei 2004 konsekutiven Melanomfällen. ERGEBNISSE: Die L/R-Ratios für kutane Nävi und Melanome betrugen 1,23 (95 %-Konfidenzintervall [KI] 1,12-1,36) sowie 1,6 (95 %-KI 1,37-1,88). Sowohl bei kutanen Nävi als auch bei Melanomen wurde der Linksüberschuss hauptsächlich in intermittierend lichtexponierter Haut gefunden. In der Nävuspopulation waren 92,4 % Rechtshänder. Die Tumordicke nach Breslow und die Ulzerationsrate waren bei linksseitigen oder rechtsseitigen primären Melanomen ähnlich. SCHLUSSFOLGERUNGEN: Melanozytäre Nävi und Melanome sind numerisch häufiger auf der linken Körperhälfte zu finden. Wir nehmen asymmetrische Sonneneinstrahlung als ursächlich an. Die große Mehrheit der Rechtshänder könnte ihre Körperhaltung bei Aktivitäten im Freien unbewusst so ausrichteten, dass das Licht von links einfällt. Dadurch wird der Schattenwurf durch den dominanten Arm, die Schulter oder den Kopf vermieden.

Direct proteomic and high-resolution microscopy biopsy analysis identifies distinct ventricular fates in severe aortic stenosis.

The incidence of aortic valve stenosis (AS), the most common reason for aortic valve replacement (AVR), increases with population ageing. While untreated AS is associated with high mortality, different hemodynamic subtypes range from normal left-ventricular function to severe heart failure. However, the molecular nature underlying four different AS subclasses, suggesting vastly different myocardial fates, is unknown. Here, we used direct proteomic analysis of small left-ventricular biopsies to identify unique protein expression profiles and subtype-specific AS mechanisms. Left-ventricular endomyocardial biopsies were harvested from patients during transcatheter AVR, and inclusion criteria were based on echocardiographic diagnosis of severe AS and guideline-defined AS-subtype classification: 1) normal ejection fraction (EF)/high-gradient; 2) low EF/high-gradient; 3) low EF/low-gradient; and 4) paradoxical low-flow/low-gradient AS. Samples from non-failing donor hearts served as control. We analyzed 25 individual left-ventricular biopsies by data-independent acquisition mass spectrometry (DIA-MS), and 26 biopsies by histomorphology and cardiomyocytes by STimulated Emission Depletion (STED) superresolution microscopy. Notably, DIA-MS reliably detected 2273 proteins throughout each individual left-ventricular biopsy, of which 160 proteins showed significant abundance changes between AS-subtype and non-failing samples including the cardiac ryanodine receptor (RyR2). Hierarchical clustering segregated unique proteotypes that identified three hemodynamic AS-subtypes. Additionally, distinct proteotypes were linked with AS-subtype specific differences in cardiomyocyte hypertrophy. Furthermore, superresolution microscopy of immunolabeled biopsy sections showed subcellular RyR2-cluster fragmentation and disruption of the functionally important association with transverse tubules, which occurred specifically in patients with systolic dysfunction and may hence contribute to depressed left-ventricular function in AS.

Influence of moisture content of frozen and embalmed human cadavers for identification of dentinal microcracks using micro-computed tomography.

The aim of this study was to investigate the influence of moisture content in frozen and embalmed human cadavers on the detection of dentinal microcracks using micro-computed tomography (micro-CT). The group of embalmed specimens included three mandibular and two maxillary segments each containing one tooth. The group of frozen cadavers consisted of two frozen mandibular bone-blocks with two teeth and one mandibular segment containing one tooth. The final number of teeth for each preservation method was n = 5. All specimens were scanned with eight different moisture conditions: 48 h wet, 2 h dry, 48 h wet, 24 h dry, 48 h wet, 1 wk dry, 48 h wet, 1 wk dry. Micro-CT images were screened for the presence of dentinal microcracks. Statistical analysis was performed by nonparametric analysis of variance (α = 5%). Only few microcracks were observed in wet and in 2 h dried bone-blocks with no significant differences (p = 0.63 and p = 0.23, respectively). There was a significant and steady increase of microcracks within the groups of dried specimens as follows: 2 h dry < 24 h dry < first wk dry < second wk dry (all p < 0.008). Preservation method had no significant influence on the visibility of microcracks (p = 0.98). Identification of dentinal microcracks on micro-CT images is influenced by moisture content of cadaveric bone-blocks irrespective of the preservation method.

Melanocytic nevi in sentinel lymph nodes: association with cutaneous nevi and clinical relevance in patients with cutaneous melanomas.

PURPOSE: Melanocytic nevi in lymph nodes (NNs) are an important histological differential diagnosis of initial sentinel lymph node (SN) metastasis in melanoma. Our aim was to associate NN in SNs with clinicopathologic features and survival rates in 1, 250 patients with SN biopsy for melanoma. METHODS: To compare patients with present and absent NN, we used Fisher's exact test, Mann-Whitney U test, and multivariate logistic regression models in this retrospective observational study based on a prospectively maintained institutional database. RESULTS: NN prevalence in axillary, cervical, and groin SNs was 16.5%, 19.4%, and 9.8%, respectively. NN were observed in combination with all growth patterns of melanoma, but more frequently when the primary was histologically associated with a cutaneous nevus. We observed a decreasing NN prevalence with increasing SN metastasis diameter. Multiple logistic regression determined a significantly increased NN probability for SNs of the neck or axilla, for individuals with ≥ 50 cutaneous nevi, midline primary melanomas, and for individuals who reported non-cutaneous malignancies in their parents. Cancer in parents was also significantly more frequently reported by melanoma patients who had more than 50 cutaneous nevi. In SN-negative patients, NN indicated a tendency for slightly lower melanoma-specific survival. CONCLUSIONS: We found a highly significant association between NN diagnosis and multiple cutaneous nevi and provided circumstantial evidence that cutaneous nevi in the drainage area of lymph nodes are particularly important. The trend toward lower melanoma-specific survival in SN-negative patients with NN suggests that careful differentiation of SN metastases is important.

Predictors of postoperative atrial fibrillation persisting beyond hospital discharge after coronary artery bypass grafting.

OBJECTIVE: Minimal invasive extracorporeal circuits (MiECC) have been associated with a significant reduction in the incidence of postoperative atrial fibrillation (AF). Nevertheless, AF remains one of the most common complications following elective primary coronary artery bypass grafting (CABG). The aim of this study was to identify the predictors of AF persisting beyond the hospital stay in elective primary CABG patients. METHODS: We conducted a retrospective analysis for the predictors of AF that persisted beyond discharge between all patients who received an elective isolated CABG in our institution between 2009 and 2014. Patients with a positive history for intermittent or persistent AF were excluded from the analysis. Almost all patients were discharged to a rehabilitation facility where they stayed for 3 to 4 weeks postoperatively. At rehab approximately 91% of them received Holter monitoring at least once prior to their discharge. RESULTS: A total of 770 patients were included in the analysis of which 763 patients survived the in-hospital stay. The incidence of AF at hospital discharge was 4.2% (32/763) while that on Holter monitor at Rehab was 1.5% (10/685). Age and the type of extracorporeal circuit (ECC) utilized were the only significant predictors for both AF at discharge (p < 0.01 both) and on Holter monitor in rehab (p < 0.01 and 0.02, respectively). This was also confirmed on multivariate analysis. CONCLUSION: Our findings show that the benefits of MiECC regarding the incidence of postoperative AF persist beyond hospital discharge. They may thus positively influence the outcomes of patients beyond the early postoperative period.

Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery.

BACKGROUND: Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques. METHODS: Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure. RESULTS: 35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively. CONCLUSION: EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.

Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches.

In rotator cuff repair, strong and reliable suturing is necessary to decrease failure rates. The biomechanics of two self-cinching stitches - the single-loop knot stitch (SLKS) and the double-loop knot stitch (DLKS) - and the modified Mason-Allen stitch (mMAS) were compared. Twenty-seven porcine infraspinatus tendons were randomized among the three stitches. Each was cyclically loaded (10-80-200 N for 50 cycles each) while the gap formation was measured. Next, ultimate load to failure was tested. The gap widths after cyclic loading were 8.72 ± 0.93 mm for the DLKS, 8.65 ± 1.33 mm for the mMAS, and 9.14 ± 0.89 mm for the SLKS, without significant differences. The DLKS showed the highest ultimate load (350.52 ± 38.54 N) compared with the mMAS (320.88 ± 53.29 N; p = 0.304) and the SLKS (290.54 ± 60.51 N; p < 0.05). The DLKS showed similar reliability and better strength compared with the mMAS, while the SLKS showed a slight but not significant decrease in performance. In our experience, the DLKS and SLKS have clinical advantages, as they are easy to perform and the self-cinching loop knot allows the surgeon to grasp degenerative tendon tissue. Initial intraoperative tightening of the suture complex (preloading) before locking is important in order to decrease postoperative elongation.

Use of symptom-focused oncological cancer therapies in hospices: a retrospective analysis.

BACKGROUND: There is controversy regarding the practical implementation of symptom-focused oncological cancer therapies to hospice residents. In this study, we aim to analyse the use and indication of supportive-oncological cancer therapies in hospices. METHODS: We conducted a retrospective survey of all residents of two hospice centres in the government district of Lower Bavaria, Germany. Hospice 1 (H1) was a member of an oncological-palliative medical network, and hospice 2 (H2) was independently organized. The evaluation period was the first 40 months after the opening of the respective hospice care centre. Demographical and epidemiological data as well as indications and type of supportive-oncological cancer therapies were recorded. A descriptive analysis and statistical tests were performed. RESULTS: Of the 706 residents, 645 had an underlying malignant disease. The average age was 72 years and the mean residence time was 28 days. The most frequent cancer types were gastrointestinal cancers, gynaecological cancers and bronchial carcinomas. Overall 39 residents (33 in H1 and 6 in H2, p < 0.01) received symptom-focused oncological cancer therapy. The average age of these residents was 68 years, and the mean residence time was 55 days. The most common therapeutic indications were dyspnoea and pain. The most common symptom-focused oncological cancer therapies were bisphosphonates, transfusions (erythrocyte- and platelet- concentrates), radiotherapy and anti-proliferative drugs (chemotherapy, anti-hormonal- and targeted- therapies). Patients with therapy lived significantly longer than patients without therapy (p < 0.01). CONCLUSIONS: Symptom-focused oncological cancer therapies can be implemented in hospices; however, their implementation seems to require certain structural and organizational prerequisites as well as careful patient selection. As a palliative medical approach, the focus is to ameliorate the symptoms and not prolong life. Symptom-focused oncology treatment could be a further and important part for the therapy of hospice patients in the future.

Gαi3 signaling is associated with sexual dimorphic expression of the clock-controlled output gene Dbp in murine liver.

The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gαi3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated genes, including Dbp. Analysis of circadian gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated genes were not affected by Gαi3 deficiency. Consistently, the period length of primary Gαi3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gαi3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in Dbp gene expression and elevated mRNA levels of the cytochrome P450 family member Cyp3a11, a target gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gαi3-pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.

MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4.

Mammalian sirtuins are involved in the control of metabolism and life-span regulation. Here, we link the mitochondrial sirtuin SIRT4 with cellular senescence, skin aging, and mitochondrial dysfunction. SIRT4 expression significantly increased in human dermal fibroblasts undergoing replicative or stress-induced senescence triggered by UVB or gamma-irradiation. In-vivo, SIRT4 mRNA levels were upregulated in photoaged vs. non-photoaged human skin. Interestingly, in all models of cellular senescence and in photoaged skin, upregulation of SIRT4 expression was associated with decreased levels of miR-15b. The latter was causally linked to increased SIRT4 expression because miR-15b targets a functional binding site in the SIRT4 gene and transfection of oligonucleotides mimicking miR-15b function prevented SIRT4 upregulation in senescent cells. Importantly, increased SIRT4 negatively impacted on mitochondrial functions and contributed to the development of a senescent phenotype. Accordingly, we observed that inhibition of miR-15b, in a SIRT4-dependent manner, increased generation of mitochondrial reactive oxygen species, decreased mitochondrial membrane potential, and modulated mRNA levels of nuclear encoded mitochondrial genes and components of the senescence-associated secretory phenotype (SASP). Thus, miR-15b is a negative regulator of stress-induced SIRT4 expression thereby counteracting senescence associated mitochondrial dysfunction and regulating the SASP and possibly organ aging, such as photoaging of human skin.