Examining the Most Impactful Strategies for In-service Preparation: A Systemic Review.

INTRODUCTION: Resident performance on the Plastic Surgery In-Service Examination (PSITE) is used as a predictor of success on the American Board of Plastic Surgery Written Examination, as well as resident progression and fellowship applications. However, information specifically addressing strategies on optimal PSITE preparation is lacking in the plastic surgery literature when compared to general surgery. For this reason, we aim to understand if the topic is well-studied and denote effective study strategies and curricular interventions in both fields that can help residents and programs optimize PSITE performance. METHODS: A literature search including studies from 2012 to 2022 was conducted following PRISMA guidelines in PubMed and EMBASE to identify articles on strategies to improve in-service exam scores for general surgery and plastic surgery. Only studies that reported measurable outcomes in raw score, percentile score, or percent correct were included. RESULTS: Qualitative analysis of 30 articles revealed 2 categories of interventions: individual study habits and institutional curricular interventions. In general surgery literature, 27 articles examined interventions positively impacting resident ABSITE scores, with 21 studies classified as institutional curricular interventions and 6 articles addressing individual study habits. Themes associated with improved ABSITE performance included mandatory remediation programs, dedicated study time, and problem-based learning interventions. In contrast, only 3 articles in plastic surgery literature discussed interventions associated with improved PSITE scores, all falling under curricular interventions. CONCLUSION: Unfortunately, the plastic surgery literature lacks concrete evidence on how residents can improve performance. Future research in plastic surgery should replicate successful strategies from general surgery and further investigate optimal preparation strategies for the PSITE. Such endeavors can contribute to improving resident performance and advancing plastic surgery education and patient care.

Neurocognitive Outcomes in Deformational Plagiocephaly: Is There an Association between Morphologic Severity and Results?

BACKGROUND: The neurodevelopmental effects of skull asymmetry and orthotic helmet therapy for deformational plagiocephaly (DP) have had limited investigation. This study assessed the long-term neurocognitive outcomes in patients with DP and their association with orthotic helmet therapy and head shape abnormality. METHODS: A total of 138 school-age children with a history of DP, 108 of whom received helmet therapy, were tested with a neurocognitive battery assessing academic achievement, intelligence quotient, and visual-motor function. Severity of presenting plagiocephaly was calculated using anthropometric and photometric measurements. Analysis of covariance was used to compare outcomes between helmeted and nonhelmeted cohorts, unilateral plagiocephaly and concomitant brachycephaly, and left-sided and right-sided plagiocephaly. The association between severity of plagiocephaly and neurocognitive outcome was assessed through a residualized change approach. RESULTS: There were no significant differences in neurocognitive outcomes between the helmeted and nonhelmeted DP cohorts or the unilateral plagiocephaly and brachycephaly cohorts. Participants with left-sided DP had significantly lower motor coordination scores than participants with right-sided DP (84.8 versus 92.7; effect size = -0.50; P = 0.03). There was a significant laterality by cephalic index interaction, with a negative association between cephalic index and reading comprehension and spelling for participants with left-sided DP. No significant associations were found between severity of presenting or posttreatment deformity and neurocognitive outcome. CONCLUSIONS: Pretreatment and posttreatment severity of plagiocephaly were not correlated with neurocognitive function at school age. Helmet therapy was not associated with better or worse long-term neurocognitive function. However, participants with left-sided DP demonstrated worse neurocognitive outcomes than participants with right-sided DP in the domains of motor coordination and some types of academic achievement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

COVID-19 Vaccination Status and Capsular Contracture Following Prosthetic Breast Reconstruction: A Retrospective, Multicenter Nested Case-Control Study.

BACKGROUND: Capsular contracture (CC) is a common long-term complication following prosthetic-based breast reconstruction (PBBR). Seven cases of CC following mRNA vaccination for coronavirus 2019 (COVID-19) are reported in the literature. OBJECTIVES: The aim of this study was to determine whether receiving the COVID-19 vaccine was associated with CC development following PBBR. METHODS: A retrospective, multicenter nested case-control study was performed from January 2014 to July 2022 of adult female patients who underwent PBBR with acellular dermal matrix placement. Cases of CC were selected if no adjuvant radiation was received and they presented for follow-up between December 2020 and July 2022. Controls included patients who met inclusion criteria but who did not experience CC in either breast. Patient demographics, breast cancer characteristics, reconstructive surgery details, postoperative complications, and COVID-19 exposure details were analyzed and correlated with CC development. RESULTS: Of a total of 230 patients (393 breasts) who received PBBR, 85 patients (135 breasts) met inclusion criteria, of whom 12 patients (19 breasts) developed CC and 73 patients (116 breasts) did not. At the time of median follow-up of 18.1 months (n = 85; interquartile range, 12.2-33.6 months), no statistically significant differences were observed between the short- or long-term complications in cases or controls. There were no significant differences in COVID-19 vaccination status, number of vaccine doses, or vaccination type between cases and controls. Vaccination status was not associated with greater odds of CC development (odds ratio, 1.44; 95% CI, 0.42-5.37; P > .05). CONCLUSIONS: Direct association between CC and COVID-19 vaccination is difficult to prove. Given the known risk of severe COVID-19 infection among immunocompromised patients, those with breast cancer who undergo PBBR should be properly counseled on the benefits and risks of vaccination.

Longitudinal Outpatient and School-Based Service Use among Children with Nonsyndromic Craniosynostosis.

BACKGROUND: Although nonsyndromic craniosynostosis has been associated with neurodevelopmental sequelae, a lesser amount of emphasis has been placed on the need for related supportive services. This study assessed the prevalence of such services among children surgically treated for nonsyndromic craniosynostosis and identified predictors of service use. METHODS: Parents of children with nonsyndromic craniosynostosis were recruited from an online craniosynostosis support network and surveyed regarding their child's use of various outpatient and school-based services. Multiple stepwise regression was performed to identify predictive variables for each type of intervention. RESULTS: A total of 100 surveys were completed. Of these, 45 percent of parents reported use of one or more outpatient support services for their children. The most commonly used services were speech therapy (26.0 percent) and physical therapy (22.0 percent), although the use of services such as psychology/psychiatry increased among older children (18.2 percent in children aged 6 to 10 years). Among school-age children ( n = 49), the majority of parents (65.3 percent) reported school-based assistance for their children, most commonly for academic (46.9 percent) or behavioral (42.9 percent) difficulties. Significant predictive variables ( p < 0.05 following stepwise regression) for increases in various outpatient and school-based services included male sex, African American race/ethnicity, higher parental income, the presence of siblings in the household, increased age at the time of surgery, and sagittal synostosis. CONCLUSIONS: Parents of children with nonsyndromic craniosynostosis reported frequent use of outpatient and school-based supportive services throughout childhood. These services may incur a significant burden of care on families. The multifactorial nature of predictive models highlights the importance of cross-disciplinary collaboration to address each child's longitudinal needs.

Spatial Analysis of the Temporomandibular Joint and Condyle Following Mandibular Distraction in Robin Sequence.

ABSTRACT: To comprehensively assess changes in temporomandibular joint and mandibular condyle morphology in Robin sequence (RS) patients undergoing mandibular distraction osteogenesis (MDO). A retrospective analysis of pediatric patients with RS and functional temporomandibular joints who underwent MDO by a single surgeon was performed. Preoperative and postoperative computed tomography (CT) scans were morphometrically analyzed three-dimensional in 3-matic and Mimics (Materialise). Comparative analysis was performed using Wilcoxon signed-rank tests. Fourteen RS patients were included (28 condyles, 56 CT scans), 78% male and 22% females. The mean age at surgery was 9.4 weeks (range 1.6-46.7 weeks). The average age at initial CT was 5.3 days (range 0-11 days). The mean time interval for CT scan before MDO and after hardware removal were 8.8 ±â€Š6.4 days and 11.2 ±â€Š25.8 days, respectively. Rotatory changes of the condyle revealed a significantly decreased horizontal angle following MDO (-7.55°, 95% confidence interval -11.13° to -3.41°; P < 0.001). Anteroposteriorly, the angle between condylar process and ramus (incline) increased significantly (14.14°, 95% confidence interval 10.71°-19.59°; P < 0.001). Intragroup analysis revealed no difference between left versus right condylar position measurements. The condyle itself increased in size and length and the intercondylion distance increased post-MDO. There were no complications and all patients achieved relief of airway obstruction without tracheostomy. Morphologic and positional changes of the mandibular condyle following MDO in RS patients parallel changes that occur during normal development in non-RS patients. As a result, MDO may facilitate normal condylar morphology and function in RS patients.

Hockey stick incision: a modified technique for chest wall masculinization.

BACKGROUND: Chest wall masculinization is often performed for transgender men in order to address gender dysphoria. Peri-areolar and double-incision mastectomy with free nipple grafts, are the most common techniques employed in chest masculinization surgery, but are limited by their relative inconsistency and inefficiency in reconstructing a natural anterior contour that comprehensively resembles that of a cis-masculine chest. The purpose of this study is two-fold. The first is to describe the "hockey stick" approach, which expands on the widely performed double-incision mastectomy to the axilla, with an additional step of revising lateral chest wall folds of tissue excess. This technique is scalable to the degree of pre-operative excess tissue on the anterior and lateral chest wall. The second is to compare the "hockey stick" incision to existing reconstructive options, with respect to clinical outcomes and patient satisfaction. METHODS: Patients who received chest masculinization surgery at Yale-New Haven Hospital were included. A retrospective chart review, comprising demographic variables, procedural details, and post-operative events, was conducted. Selected modules from a validated survey instrument, the BODY-Q, were measured. Patients were classified by body mass index and incision, which included peri-areolar, inframammary fold, and "hockey stick" incision by date. RESULTS: Twenty-seven of 73 (37.0%) participants completed the full survey and were included in the analysis. The "hockey stick" incision had comparable patient satisfaction and post-operative outcomes, compared to peri-areolar and double-incision mastectomy with free nipple graft techniques. Greater BMI patients had a higher incidence of wound dehiscence, compared to other weight classifications. CONCLUSIONS: The "hockey stick" incision is a readily performed, effective surgical technique for building a cis-masculine appearing chest in transgender men with efficient and predictable outcomes. While performed in patients with higher BMI, the "hockey stick" confers equivalent patient satisfaction and clinical outcomes to peri-areolar and double-incision mastectomy.

Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

INTRODUCTION: Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS: Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS: Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. CONCLUSION: Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Neurological Functional Connectivity in Unilateral Coronal Synostosis: A Side-Based Comparison.

PURPOSE: Unicoronal synostosis (UCS) has been associated with reading, language, and social dysfunction. Limited brain function connectivity studies exist for UCS with none devoted to comparing outcomes by side of synostosis (left versus right-sided UCS). METHODS: Twelve patients with surgically treated UCS, 7 right-sided and 5 left-sided, were age matched to healthy controls. Resting state functional MRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis using BioImage Suite (Yale School of Medicine). Region of interest analysis was performed based on Brodmann areas related to emotional, executive, language, motor, and visuo-spatial function. Significance was set at P < 0.05. RESULTS: Compared to controls, all UCS patients demonstrated decreased connectivity in areas of the parietal and temporal cortices responsible for visuo-motor coordination and language function. Right UCS patients demonstrated decreased intrinsic connectivity in regions related to complex motor movement and proprioception relative to control subjects. Left UCS patients demonstrated decreased seed connectivity between regions of the parietal lobe and occipital lobe related to motor coordination, visual function, and language compared to right UCS patients. CONCLUSION: Unicoronal synostosis had decreased functional connectivity in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits for motor coordination and language when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may be responsible for neurocognitive impairments found in previous cognitive analyses.

The Effect of Surgical Timing on 30-Day Outcomes in Cleft Palate Repair.

BACKGROUND: The optimal age for cleft palate repair continues to be debated, with little discussion of surgical risk related to operative timing. This study of 3088 cleft palate patients analyzed the impact of surgical timing on perioperative and 30-day postoperative outcomes. METHODS: Primary cleft palate repairs were identified in the National Surgical Quality Improvement Program database from 2012 to 2015. Data were combed for total postoperative complications, rates of readmission and reoperation, operating room time, and length of stay. Bivariate analyses were performed comparing 3-month periods from months 6 to 18, and months 0 to 5, 18 to 23, 24 to 29, and 30 to 59. RESULTS: Despite a higher proportion of isolated soft palate closure, children operated on before 6 months had a higher complication rate than children at other ages (7.1 percent versus 3.2 percent; OR, 2.4; p = 0.04), and higher rates of both readmission (3.6 percent versus 1.4 percent; OR, 3.6; p = 0.02) and reoperation (2.4 percent versus 0.5 percent; OR, 4.7; p = 0.04). There were no differences in short-term outcomes for any other age group younger than 5 years, and no differences in hospital length of stay among any age groups. CONCLUSIONS: The authors' findings suggest a relative contraindication to operation before 6 months. As there were no differences between any other age groups, long-term speech optimization should continue to be the primary consideration for operative planning. These findings improve the current rationale for palatoplasty timing, and can aid surgeons and parents in the surgical decision-making process. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Comparison of Neurocognitive Outcomes in Postoperative Adolescents with Unilateral Coronal Synostosis.

Unilateral coronal nonsyndromic craniosynostosis is associated with asymmetric skull growth, which may influence cerebral long-term function. Twenty affected adolescents who underwent cranial vault remodeling at a mean age of 8.2 months (12 from the Yale Craniofacial Clinic and eight from the Children's Hospital of Philadelphia) all completed a double-blinded neurodevelopmental assessment at an average age of 12.1 years. The study cohort included 55 percent female and 50 percent right-sided craniosynostosis. Mean verbal intelligence quotient was highest at 117.3, and mean performance intelligence quotient was 106.4, for a mean full-scale intelligence quotient of 112.5. Patients performed above the national average on all academic achievements except for numerical operations, which was significantly lower than word reading (p = 0.022). Patients performed below average on all Beery-Buktenica visual motor tests; motor-coordination was poorer than both visual motor integration and visual perception (p = 0.027 and p = 0.005). Significant positive correlations existed between paternal education/visual perception (r = 0.450; p = 0.046) and household income/verbal intelligence quotient (r = 0.628; p = 0.004). Patients with right unilateral coronal nonsyndromic craniosynostosis had improved spelling compared with left-sided patients on multivariate regression (p = 0.033). Female patients had higher motor coordination (p = 0.024). Breast-fed patients had better performance intelligence quotient (p = 0.024), visual motor integration (p = 0.014), and visual perception (p = 0.031). Adolescents who underwent cranial vault remodeling at two institutions had above average intelligence quotient scores, but worse mathematical and visual motor achievement compared with control subjects. Left-side craniosynostosis patients performed worse in spelling than right-side patients. Breast-feeding was an independent predictor for improved performance intelligence quotient, visual motor achievement, and visual perception performance. Study findings are limited by the cohort size. A larger population study is required, which could validate or modify the study conclusions.

Radiographic Severity of Metopic Craniosynostosis Correlates with Long-Term Neurocognitive Outcomes.

BACKGROUND: Reports of neurodevelopmental delays in adolescents with metopic craniosynostosis have ranged from 15 to 61 percent. Previously, event-related potentials have correlated preoperative radiographic severity with language deficiencies in infancy. This study sought to characterize neurocognitive testing at cranial maturity and correlate outcomes to preoperative radiographic severity. METHODS: Patients diagnosed with metopic craniosynostosis who underwent surgical correction in infancy completed a neurodevelopmental battery evaluating age-normalized intelligence quotient, academic achievement, and visuomotor integration. Data were stratified by preoperative endocranial bifrontal angle (moderate, >124 degrees; severe, <124 degrees). Multiple variable regression was used to control measured intelligence and achievement for age at surgery, age at testing, parental education, and income. Significance was set at p < 0.05. RESULTS: Twenty patients completed neurodevelopmental testing. Mean intelligence quotient was 111.7 ± 13 and academic achievement was similar to national averages (word reading, 53.4 percent; reading comprehension, 53.4 percent; reading composite, 53.5 percent; spelling, 44 percent; and math, 52.9 percent). Radiographic measurements revealed 36 percent of patients with moderate phenotype and 64 percent with severe. Patients with severe phenotypes had lower intelligence quotient measures and scored more poorly in every academic measure tested. Word reading (113 versus 95; p = 0.035) and reading composite (109 versus 98; p = 0.014) reached significance. CONCLUSIONS: Overall, cranial mature patients with metopic craniosynostosis had above average intelligence quotient and academic achievement near the national mean. Long-term neurocognitive function was correlated to preoperative radiographic severity in metopic craniosynostosis, with more severe cases performing worse. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Assessing Facial Asymmetry in Postoperative Patients With Unilateral Coronal Craniosynostosis.

BACKGROUND: Despite surgical correction of unilateral craniosynostosis (ULC), complex cranial base angulation can result in partial reversion to preoperative deformity with growth and time. Using 3-dimensional imaging, dysmorphic facial features of ULC in school-age patients were quantified and related to how they contribute to overall facial asymmetry and patient-reported outcomes. METHODS: Children who underwent surgical correction of ULC were recruited from Yale University and Children's Hospital of Philadelphia. The 3D photographs were analyzed utilizing a Procrustes analysis of shape. Pearson's correlation was used to determine dysmorphic features' impact on overall asymmetry. Patients were stratified into "moderate" and "severe" asymmetry. Finally, asymmetry was correlated to patient-reported outcome scores. Statistical analysis was performed with SPSS-25 with P < 0.05 as statistically significant. RESULTS: Twenty-one patients were included with average age at analysis of 12.3 years. Fifty-seven percent of patients had right-sided fusion. The overall Procrustes analysis indicated a root mean square difference of 2.21 mm. Pearson's correlation indicated that the facial middle 3rd (P ≤ 0.001), orbital dystopia (P < 0.001), chin point deviation (P = 0.011), and nasal root angulation (P = 0.019) contributed most to overall asymmetry. Patients in the severe asymmetry cohort had greater facial middle-third asymmetry (P < 0.001) and orbital dystopia (P < 0.001). Asymmetry did not correlate with patient-reported outcomes. CONCLUSION: Patients with ULC have persistent facial asymmetry at school-age with the greatest levels of asymmetry in the facial middle-third, orbit, and nasal root. Beyond the cranial dysmorphology, initial skull base angulation in unilateral coronal craniosynostosis manifests in long-term mid and lower-third facial asymmetry.

Rhinoplasty Using Three-Dimensional Analysis and Simulation.

Treatment of nasal deformity and obstruction requires analysis, planning, and precise execution of rhinoplasty techniques. When performed well, rhinoplasty is a powerful tool for achieving appealing nasal morphology and optimizing function. This article aims to highlight an open approach to septorhinoplasty using a number of techniques that are preferred by the senior author (D.M.S.) to successfully correct a congenital nasal deformity and deviated septum.

Correction of Sagittal Synostosis Using Three-Dimensional Planning and Maltese Cross Geometry.

There are several approaches to correct sagittal synostosis. Regardless of technique, the goals are to (1) release the fused suture and (2) impart a normocephalic head shape with resultant functional and aesthetic benefits. This article and video detail the authors' preferred technique for the treatment of sagittal synostosis. This novel method involves three-dimensional planning and an open approach to focus on immediate correction of the anteroposterior, mediolateral, and vertex dimensions, using vault remodeling, pedicled osseous ("Maltese") crosses, and corset pericranial flaps.

What Is the Skull Structure Influence of Squamosal Suture Synostosis in Nonsyndromic and Syndromic Crouzon Craniosynostosis?

BACKGROUND: The morphologic effect of squamosal synostosis has not been clarified, due to its low occurrence rate, and its inclination to be combined with premature closure of other major sutures, especially in syndromic synostosis. This study's goal is to explore the morphological influence of squamosal synostosis in both syndromic and nonsyndromic craniosynostosis patients. METHODS: Twenty-five computed tomography (CT) scans from nonsyndromic squamosal synostosis (NSS), Crouzon syndrome with squamosal synostosis (CSS), Crouzon syndrome without squamosal synostosis, and normal controls were included. Three-dimensional (3D) cephalometry, entire cranial volume and cranial fossa volume were measured using Materialise software. RESULTS: The entire cranial volume of all groups was similar. The NSS developed a gradual reduction in the severity of reduced segmental volume from the anterior cranial fossa, to the middle cranial fossa, and to the unaffected volume of posterior cranial fossa. The CSS developed the most severe volume reduction of middle cranial fossa (12608.30 ±â€Š2408.61 mm vs 26077.96 ±â€Š4465.74 mm, 52%), with proportionate volume reduction of the anterior (7312.21 ±â€Š2435.97 mm vs 10520.63 ±â€Š2400.43 mm, 30%) and posterior cranial fossa (33487.29 ±â€Š5598.93 mm vs 48325.04 ±â€Š14700.44 mm, 31%). The NSS developed a narrower anterior cranial fossa, a clockwise rotated Frankfort horizontal plane, and a retracted chin (pogonion). CONCLUSION: Squamosal synostosis may alter the development of cranial fossa volume, especially the volume of middle cranial fossa. However, the development of cranial base, and related facial features are determined largely by major vault sutures and associated syndromic conditions, rather than the squamosal suture alone. LEVEL OF EVIDENCE: II.

Liraglutide modulates adipokine expression during adipogenesis, ameliorating obesity, and polycystic ovary syndrome in mice.

PURPOSE: The incidence of obesity is increasing among all age groups throughout the world and it is highly associated with numerous other metabolic disorders, such as insulin resistance, polycystic ovarian syndrome (PCOS) etc. METHODS AND RESULTS: Using in vitro and in vivo approach, this study investigated the adipokine profile after liraglutide on differentiated murine 3T3-L1 pre-adipocytes. Effect of liraglutide on DHEA-induced PCOS mice were investigated. This study showed Liraglutide treatment resulted in up-regulation of adiponectin and IL-6 along with down-regulation of ICAM 1 in differentiated 3T3-L1 cells. Liraglutide in absence of other differentiating factors, significantly increased glucose, lipid uptake and PPARγ, C/EBPα expression in the adipocytes suggesting its ability to solely promote pre-adipocyte differentiation into mature adipocyte. Liraglutide treatment showed increased adiponectin expression and decreased number of cystic follicles, body weight, circulating glucose, triglyceride and testosterone levels in comparison to the PCOS induced mice. CONCLUSION: This study suggests that adiponectin may act as a link between metabolic disorders and PCOS and that liraglutide might be a promising therapeutic agent for the treatment of PCOS in addition to obesity and insulin resistance.

Adiponectin and Chemerin: Contrary Adipokines in Regulating Reproduction and Metabolic Disorders.

Metabolic disorders such as obesity and type 2 diabetes are one of the most familiar risk factors in the present time among every age-group. It is associated with altered levels of adipokines such as adiponectin, chemerin, leptin, resistin, visfatin, and so on. Adiponectin is one of the adipocyte-specific protein with novel applications pertaining to metabolism by promoting insulin sensitivity and regulating glucose and fatty acid catabolism, while chemerin is considered as an inhibitor of insulin signaling and glucose catabolism. Other than these established functions, both the adipokines are intimately involved in coordinating reproductive activities, but they exhibit contrary functions. This review is an amalgamation of recent information related to adiponectin and chemerin in male and female reproduction and further its association with metabolism-related reproductive disorders. The direct effect of adiponectin and chemerin on various reproductive parameters has been investigated, but there was a rampant failure to account for in vivo data which gives a broad outlook on the regulatory mechanism of both adiponectin and chemerin related to male and female reproductive functions. Adiponectin is known to promote gonadal activities, while chemerin exerts antigonadal actions. Recent research suggests that high chemerin/low adiponectin ratio plays a vital role in causing dyslipidemia and metabolic syndrome in patients. The dysregulated ratio of adiponectin to chemerin during various metabolic disorders makes it really worthy in relation to an application for therapeutics. Still, a lot regarding both the adipokines has to be explored and brought forward in order to deal with therapeutics of metabolism-related reproductive disorders.

Systemic adiponectin treatment reverses polycystic ovary syndrome-like features in an animal model.

The present study examined the efficacy of adiponectin for regulating the reproductive, metabolic and fertility status of mice with polycystic ovary syndrome (PCOS). PCOS was induced in prepubertal (21- to 22-day-old) mice using dehydroepiandrosterone (6mg 100g-1day-1 for 25days), after which mice were administered either a low or high dose of adiponectin (5 or 15µgmL-1, s.c., respectively). PCOS mice exhibited typical features, including the presence of numerous cystic follicles, increased circulating androgens, increased body mass, altered steroidogenesis, decreased insulin receptor expression and increased serum triglycerides, serum glucose, Toll-like receptor (TLR)-4 (a marker of inflammation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis). These parameters were significantly correlated with a reduction in adiponectin in PCOS mice compared with vehicle-treated control mice. Exogenous adiponectin treatment of PCOS mice restored body mass and circulating androgen, triglyceride and glucose levels. Adiponectin also restored ovarian expression of steroidogenic markers (LH receptors, steroidogenic acute regulatory protein and 3ß-hydroxysteroid dehydrogenase), insulin receptor, TLR-4 and VEGF levels in control mice. Adiponectin restored ovulation in PCOS mice, as indicated by the presence of a corpus luteum and attainment of pregnancy. These findings suggest that adiponectin effectively facilitates fertility in anovulatory PCOS. We hypothesise that systemic adiponectin treatment may be a promising therapeutic strategy for the management of PCOS.