Unaffected Subjects Research Articles

Involvement of the nuclear factor-\u03baB transcriptional complex in prefrontal cortex immune activation in bipolar disorder

Bipolar disorder and schizophrenia have multiple clinical and genetic features in common, including shared risk associated with overlapping susceptibility loci in immune-related genes. Higher activity of the nuclear factor-κB (NF-κB) transcription factor complex, which regulates the transcription of multiple immune markers, has been reported to contribute to immune activation in the prefrontal cortex in schizophrenia. These findings suggest the hypothesis that elevated NF-κB activity is present in the prefrontal cortex in bipolar disorder in a manner similar to that seen in schizophrenia. Therefore, we quantified levels of NF-κB-related mRNAs in the prefrontal cortex of 35 matched pairs of bipolar disorder and unaffected comparison subjects using quantitative PCR. We found that transcript levels were higher in the prefrontal cortex of bipolar disorder subjects for several NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs, and were lower for an NF-κB inhibitor. Transcript levels for NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs levels were also highly correlated with each other. This pattern of elevated transcript levels for NF-κB-related markers in bipolar disorder is similar to that previously reported in schizophrenia, suggesting that cortical immune activation is a shared pathophysiological feature between the two disorders.

A prospective study to evaluate accuracy of urine albumin-creatinine ratio in diagnosis of pre-eclampsia; A single centre observational study

The aim of this paper is to diagnose pre-eclampsia with spot urine albumin-creatinine ratio (ACR). Our study comprised of one hundred ten pregnancies within 20-28 weeks of gestation. Spot mid- stream urine sample was collected from all pregnant females and urine ACR estimation was done using immunoturbidimetric microalbumin method and modified Jaffe’s method for creatinine estimation. We found sensitivity of 90.4%, specificity of 98%, PPV of 91.6% and NPV of 97.2%. Systolic blood pressure in unaffected subjects was 110.2 mm Hg and in pre- eclamplsia was 152.6 mm Hg. Diastolic blood pressure in unaffected subjects was 78.4 mm Hg and in pre- eclamplsia was 96.8 mm Hg. In unaffected subjects, 4.5% showed positive test and 95.5% showed negative test. In pre- eclampsia subjects, 87.2% showed positive test and 12.8% showed negative test. Mann Whitney U test showed significant difference between two (Significant, P< 0.05). It has been observed that the role of urine albumin creatinine ratio in detection of Pre-eclampsia is evident. A higher sensitivity and specificity revealed its usefulness in early detection.

A Three-Dimensional Comparison of Nasolabial Soft Tissue between Children with Repaired Unilateral Complete Cleft Lip and Palate and Unaffected Children in Khon Kaen, Thailand.

The objectives were to assess the treatment outcomes of unilateral cleft lip and palate after primary surgery on nasolabial soft tissue of children ages 4-5 years old as compared with unaffected children and to establish a nasolabial soft tissue norm within Khon Kaen. This cross-sectional study consisted of 60 unaffected subjects living in Khon Kaen province and 20 subjects with repaired complete unilateral cleft lip and palate who were treated at Srinagarind Hosipital, Khon Kaen, Thailand. 3D images were taken by a Morpheus 3D Scanner and measured by the Morpheus 3D program. Independent t-tests and paired t-tests were used to analyze the significant differences between subjects with cleft and unaffected subjects. There were statistically significant differences (p<0.05) of nasolabial measurements between affected subjects and unaffected subjects. Unilateral measurements showed decreased nostril height, columella lengths, and nose protrusion from ala base and ala length in the affected group. In addition, bilateral measurements found decreased upper lip protrusion, philtrum length, upper lip height, upper vermillion thickness, and lip angle. This study attempted to establish a norm for evaluating the treatment outcome of cleft lip and cleft palate repair at Srinagarind Hospital in relation to unaffected or noncleft individuals. The results suggest that the noncleft side in affected patients is not an optimal surgical guide for cleft repair and the surgeon should correct both sides of lip and nose features according to the norms. A surgical treatment plan should emphasize correcting nostril height, columella length, nose protrusion from ala base, ala length, and upper lip features.

Alterations in plasma kynurenine pathway metabolites in children and adolescents with bipolar disorder and unaffected offspring of bipolar parents: A preliminary study.

There has been growing scientific evidence in recent years that bipolar disorder (BD) is associated with alterations in the kynurenine (KYN) pathway. However, many of these studies have been limited by their focus on adults. Thus, this preliminary study investigated differences in the peripheral levels of KYN metabolites in children and adolescents with BD, unaffected offspring of parents with BD, and healthy controls (HCs). Plasma samples were collected from 49 youths with BD, 19 bipolar offspring, and 31 HCs. Tryptophan (TRP), KYN, and kynurenic acid (KYNA) were separated using electrospray ionization. One-Way ANCOVA after controlling for age, gender, race, BMI-for-age, and smoking status showed that BD had lower levels of KYN, while unaffected high-risk offspring subjects had lower levels of TRP, KYN, and KYNA when compared to HCs. Moreover, we found that KYN, KYN/TRP, and KYNA/KYN levels predicted the severity of depressive symptoms, while the YMRS score was not associated with any metabolite. In summary, this preliminary study has shown that KYN metabolites are decreased in both affected and unaffected subjects, strengthening the idea that the KYN pathway might underlie the familial risk of BD shown by high-risk offspring individuals. However, longitudinal studies are needed to examine whether the alterations observed in this study represent early markers of risk for later developing BD.

Automated syndrome diagnosis by three-dimensional facial imaging

PurposeDeep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face is affected in 30–40% of known genetic syndromes. Here, we determine whether syndromes can be diagnosed from 3D images of human faces. MethodsWe analyzed variation in three-dimensional (3D) facial images of 7057 subjects: 3327 with 396 different syndromes, 727 of their relatives, and 3003 unrelated, unaffected subjects. We developed and tested machine learning and parametric approaches to automated syndrome diagnosis using 3D facial images. ResultsUnrelated, unaffected subjects were correctly classified with 96% accuracy. Considering both syndromic and unrelated, unaffected subjects together, balanced accuracy was 73% and mean sensitivity 49%. Excluding unrelated, unaffected subjects substantially improved both balanced accuracy (78.1%) and sensitivity (56.9%) of syndrome diagnosis. The best predictors of classification accuracy were phenotypic severity and facial distinctiveness of syndromes. Surprisingly, unaffected relatives of syndromic subjects were frequently classified as syndromic, often to the syndrome of their affected relative. ConclusionDeep phenotyping by quantitative 3D facial imaging has considerable potential to facilitate syndrome diagnosis. Furthermore, 3D facial imaging of “unaffected” relatives may identify unrecognized cases or may reveal novel examples of semidominant inheritance.

First Trimester DEX Treatment Is Not Associated with Altered Brain Activity During Working Memory Performance in Adults.

ContextPrenatal dexamethasone (DEX) treatment is sometimes used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in female fetuses with CAH. In boys and in fetuses not having CAH, there is no benefit of early DEX treatment and the risks of this therapy must be thoroughly investigated. High doses of prenatal glucocorticoid might alter the developmental trajectory of the brain into adulthood, even for CAH unaffected subjects treated with DEX for a short term during the first trimester.ObjectiveThe present study investigated brain activation during working memory performance in DEX-treated subjects compared with controls.Design, Setting, and ParticipantsWe tested 18 participants who were exposed to DEX during the first trimester of fetal life but did not have CAH (8 females; mean age 20.78 [standard deviation (SD), 2.67] years) and 40 control participants (24 females; mean age 20.53 [SD, 2.64]) from a single research institute. Participants underwent functional magnetic resonance imaging on a 3T scanner during a verbal and visuospatial working memory task.ResultsWe did not observe any differences in brain activity during working memory performance. However, DEX-treated subjects responded faster during the experimental condition of the verbal WM task.ConclusionsFirst trimester DEX treatment did not seem to result in altered working memory–related brain activity at adult age. Our findings contribute to the risk–benefit assessment of prenatal DEX treatment in the context of CAH.

Urinary 1H-NMR Metabolic Signature in Subjects Undergoing Colonoscopy for Colon Cancer Diagnosis

Metabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests.

A clinical and multi‑omics study of Van der Woude syndrome in three generations of a Chinese family.

Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4-month-old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three-generation family were subsequently collected, and whole-exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole-transcriptome sequencing, expression analysis and Gene Ontology enrichment analysis were conducted on two groups of patients with phenotypic diversity from the same family. These analyses identified significant differentially expressed genes and enriched pathways in these two groups. Altogether, these findings provide insight into the mechanism underlying the variable expressivity of VWS.

Deficits in Glutamic Acid Decarboxylase 67 Immunoreactivity, Parvalbumin Interneurons, and Perineuronal Nets in the Inferior Colliculus of Subjects With Schizophrenia.

Aberrant processing of auditory stimuli is a prominent feature of schizophrenia (SZ). Prior studies have chronicled histological abnormalities in the auditory cortex of SZ subjects, but whether deficits exist at upstream, subcortical levels has yet to be established. En route to the auditory cortex, ascending information is integrated in the inferior colliculus (IC), a highly gamma amino butyric acid (GABA) ergic midbrain structure that is critically involved in auditory processing. The IC contains a dense population of parvalbumin-immunoreactive interneurons (PVIs), a cell type characterized by increased metabolic demands and enhanced vulnerability to oxidative stress. During development, PVIs are preferentially surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures that promote redox homeostasis and excitatory/inhibitory balance. Moreover, in SZ, deficits in PVIs, PNNs, and the GABA synthesizing enzyme, glutamic acid decarboxylase (Gad67), have been extensively documented in cortical regions. Yet, whether similar impairments exist in the IC is currently unknown. Thus, we compared IC samples of age- and sex-matched pairs of SZ and unaffected control subjects. SZ subjects exhibited lower levels of Gad67 immunoreactivity and a decreased density of PVIs and PNNs within the IC. These findings provide the first histological evidence of IC GABAergic abnormalities in SZ and suggest that SZ-related auditory dysfunction may stem, in part, from altered IC inhibitory tone.

Interocular asymmetry of foveal avascular zone morphology and parafoveal capillary density in sickle cell retinopathy.

ObjectivesTo examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A).MethodsThis cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR—including non-proliferative SCR (NP-SCR) and proliferative SCR (P-SCR)–and unaffected controls.ResultsThirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and age-matched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics.ConclusionsNP-SCR and P-SCR patients demonstrated quantifiable interocular asymmetry in FAZ and parafoveal capillary density metrics compared to unaffected subjects, with left-eye predominance in disease severity.

The Montreal Cognitive Assessment (MoCA) and Brain Structure

Abstract. MoCA is a short cognitive screening tool. We examined the relationship of MoCA performance to white matter integrity, gray matter volume, and surface-based measurements at normal aging in a study in which older and younger cognitively unaffected subjects participated. The sample was split according to MoCA performance, and the data were analyzed using a general linear model (Age × MoCA). We found effects in the expected direction for all methods. The main effects on age and performance as well as interactions occurred for regions associated with aging, pathological and nonpathological. Older low-performing subjects showed structural deficits compared to older high-performing subjects. Therefore, the global index of cognitive status reflects relevant features of the brain structure.

Evidence of a Recessively Inherited CCN3 Mutation as a Rare Cause of Early-Onset Parkinsonism.

The study of consanguineous families has provided novel insights into genetic causes of monogenic parkinsonism. Here, we present a family from the rural Khyber Pakhtunkhwa province, Pakistan, where three siblings were diagnosed with early-onset parkinsonism. Homozygosity mapping of two affected siblings and three unaffected family members identified two candidate autozygous loci segregating with disease, 8q24.12-8q24.13 and 9q31.2-q33.1. Whole-exome sequence analysis identified a single rare homozygous missense sequence variant within this region, CCN3 p.D82G. Although unaffected family members were heterozygous for this putative causal mutation, it was absent in 3,222 non-Parkinson's disease (PD) subjects of Pakistani heritage. Screening of 353 Australian PD cases, including 104 early-onset cases and 57 probands from multi-incident families, also did not identify additional carriers. Overexpression of wild-type and the variant CCN3 constructs in HEK293T cells identified an impaired section of the variant protein, alluding to potential mechanisms for disease. Further, qPCR analysis complemented previous microarray data suggesting mRNA expression of CCN3 was downregulated in unrelated sporadic PD cases when compared to unaffected subjects. These data indicate a role for CCN3 in parkinsonism, both in this family as well as sporadic PD cases; however, the specific mechanisms require further investigation. Additionally, further screening of the rural community where the family resided is warranted to assess the local frequency of the variant. Overall, this study highlights the value of investigating underrepresented and isolated affected families for novel putative parkinsonism genes.

X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion of ALAS2.

BackgroundX-linked dominant protoporphyria (XLDPP) is a rare, hereditary disorder that leads to hepatobiliary and hematologic abnormalities including increased erythrocyte protoporphyrin, cutaneous photosensitivity, and decreased iron stores that is caused by a pathogenic mutation of ALAS2 gene.MethodsThis study aimed to confirm the existence of XLDPP in a Chinese pedigree. We observed and described the dermatoscopic findings of this disorder under dermoscopy, and assessed photo damage in XLDPP patients using the Fotofinder system and very high frequency (VHF) skin ultrasonic system. We performed next generation sequencing and Sanger sequencing to detect and confirm genetic variants in DNA samples from the XLDPP family. Moreover, we monitored the hepatobiliary function as well as hematologic changes in related family members.ResultsAs compared to unaffected control subjects, patients exhibited evidence of severe cutaneous photodamage, causing photoaging, an increase in the size of the gallbladder, increased levels of protoporphyrin in red blood cells, an increase in blood levels of uroporphyrin and hematoporphyrin, and iron deficiency.ConclusionsXLDPP was validated by the identification of a four-base-pair deletion (c.1706_1709delAGTG, p.E569fs) in ALAS2 (NM_000032.4) in the proband which segregated with the disease in an X-linked dominant pattern, with hemizygous males being more severely affected than heterozygous females. We also found a missense variant in GATA Binding Protein 1 (GATA1).

Disease burden and treatment considerations in Krabbe disease: The caregiver perspective

The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ε4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patterns between AD-affected and -unaffected whites (2673/16,246), Hispanics (392/867), and African Americans (285/1789), separately. We focused on 29 polymorphisms from 5 genes in the APOE region emphasizing beneficial and adverse effects of the APOE ε2- and ε4-coding single-nucleotide polymorphisms, respectively, and the differences in the linkage disequilibrium structures involving these alleles between AD-affected and -unaffected subjects. Susceptibility to AD is likely the result of complex interactions of the ε2 and ε4 alleles with other polymorphisms in the APOE region, and these interactions differ across races/ethnicities corroborating differences in the adverse and beneficial effects of the ε4 and ε2 alleles. Our findings support complex race/ethnicity-specific haplotypes promoting and protecting against AD in this region. They contribute to better understanding of polygenic and resilient mechanisms, which can explain why even homozygous ε4 carriers may not develop AD.

Italian Men Tested for BRCA1/2 Mutation: Psychological Distress during 6-Month Follow-Up.

Introduction. Male breast cancer (MBC) is a rare disease, whose main risk factor is genetic vulnerability. Despite care of men with MBC is modeled on care of women, men's experiences with the disease and concerns related to the status of genetic mutation carrier are unique. So far, little is known concerning the psychological impact in BRCA1/2 testing, especially with regard to specific subset of individuals, such as male subjects and the elderly. Methods We assessed self-reported anxiety and depression levels in 26 male subjects presenting at Unit of Breast Surgery in Breast Unit of AOUI Verona (MBC patients, n = 7; high-risk unaffected subjects, n = 7; high-risk unaffected subjects, Results Among the 17 unaffected men tested, 7 (41%) received a positive test (either BRCA1 or BRCA2 pathogenic variant) and 10 (59%) a negative test. Of the 9 MBC patients tested, only one subject received a positive test result. No significant differences were observed in mean scores, mean change from baseline to follow-up, either for those with T+ or T− test results. Discussion. Genetic testing for BRCA1/2 mutation was not associated in our sample with increased level of psychological distress as measured with HADS in a short-term evaluation.

The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after exposure to severe psychological trauma, leaving patients with disabling anxiety, nightmares, and flashbacks. Current treatments are only partially effective, and development of better treatments is hampered by limited knowledge of molecular mechanisms underlying PTSD. We have discovered that the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP51) form a protein complex that is elevated in PTSD patients compared with unaffected control subjects, subjects exposed to trauma without PTSD, and patients with major depressive disorder (MDD). The GR-FKBP51 complex is also elevated in fear-conditioned mice, an aversive learning paradigm that models some aspects of PTSD. Both PTSD patients and fear-conditioned mice had decreased GR phosphorylation, decreased nuclear GR, and lower expression of 14-3-3ε, a gene regulated by GR. We created a peptide that disrupts GR-FKBP51 binding and reverses behavioral and molecular changes induced by fear conditioning. This peptide reduces freezing time and increases GR phosphorylation, GR-FKBP52 binding, GR nuclear translocation, and 14-3-3ε expression in fear-conditioned mice. These experiments demonstrate a molecular mechanism contributing to PTSD and suggest that the GR-FKBP51 complex may be a diagnostic biomarker and a potential therapeutic target for preventing or treating PTSD.

Association of MAPK4 and SOX1-OT gene polymorphisms with cleft lip palate in multiplex families: A genetic study.

Background. Cleft lip and palate (CLP) is a common congenital anomaly. Many genes, like MAPK4 and SOX-1OT, are associated with its etiology in different populations. High-risk markers on these gene sreported in other populations were not studied in our population. Hence, the study aimed to determine the association of MAPK4 and SOX-1OT polymorphisms in CLP in multiplex families. Methods. Based on inclusion and exclusion criteria, we selected 20 multiplex CLP families for this case‒control study, in which the affected individuals and healthy controls selected from these families were compared. Fifty subjects affected with cleft and 38 unaffected subjects were included in the study. The polymorphisms studied for the association consisted of rs726455 and rs2969972 in the genes SOX-1 OT and MAPK4, respectively. DNA was isolated and sent for genotyping using the MassArray method. Plink, a whole-genome association analysis toolset, was used for statistical analysis. Results. Both polymorphisms followed Hardy–Weinberg equilibrium. The rs726455 of SOX-1OT yielded a P-value of 0.983 and an allelic odds ratio (OR) of 0.983. For rs2969972 of MAPK4, the P-value was 0.04 (significant), and the allelic OR was 0.51. Minor allele frequency (MAF) in the unaffected subjects was more than the MAF in the affected subjects for rs2969972. Conclusion. The results suggested that polymorphism rs726455 on SOX-1OT was not associated with familial cases of CLP. Since MAF in the unaffected subjects was more than the MAF-affected subjects, rs2969972 on MAPK4 is protective in the multiplex families.

Genetic and regulatory architecture of Alzheimer's disease in the APOE region.

IntroductionApolipoprotein E (APOE) ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro “risk” factors for Alzheimer's disease (AD).MethodsWe examined differences in linkage disequilibrium (LD) structures between (1) AD‐affected and unaffected subjects and (2) older AD‐unaffected and younger subjects in the 19q13.3 region harboring rs7412 and rs429358.ResultsAD is associated with sex‐nonspecific heterogeneous patterns of decreased and increased LD of rs7412 and rs429358, respectively, with other polymorphisms from five genes in this region in AD‐affected subjects. The LD patterns in older AD‐unaffected subjects resembled those in younger individuals. Polarization of the ε4‐ and ε2 allele–related heterogeneous LD clusters differentiated cell types and implicated specific tissues in AD pathogenesis.DiscussionProtection and predisposition to AD is characterized by an interplay of rs7412 and rs429358, with multiple polymorphisms in the 19q13.3 region in a tissue‐specific manner, which is not driven by common evolutionary forces.

Evaluation of Biomechanically Corrected Intraocular Pressure Measurements in Keratoconus and Forme Fruste Keratoconus

Introduction: Although biomechanically corrected intraocular pressure (bIOP) is available, the effectiveness of intraocular pressure (IOP) correction in keratoconus and forme fruste keratoconus (FFK) eyes has not been investigated. Objective: Evaluation of bIOP measurements in eyes with keratoconus and FFK. Methods: Forty-two eyes in 21 patients with keratoconus in one eye and FFK in the fellow eye were examined (KC/FFK group; mean age 24.62 ± 8.6 years; 16 males and 5 females). The control group consisted of 62 eyes in 31 unaffected subjects (mean age 26.26 ± 3.64 years; 15 males and 16 females). The bIOP was determined using a Scheimpflug-based tonometer (Corvis Scheimpflug Technology [Corvis ST®]) after measuring the IOP with a conventional non-contact tonometer (NIOP). The agreement between NIOP and bIOP values was examined using the Bland-Altman plot. The difference between NIOP and bIOP (bIOP correction amount) was compared between keratoconus and FFK eyes. Results: In the control group, there were no significant differences between right and left eyes in both NIOP and bIOP values (p = 0.975 and p = 0.224, respectively). In the KC/FFK group, NIOP values were significantly lower in the keratoconus eyes (9.93 ± 1.96 mm Hg) than in the FFK eyes (12.23 ± 3.03 mm Hg; p = 0.0003). There was no significant difference in bIOP values between the right and left eyes of the KC/FFK group (p = 0.168). The bIOP correction amount was significantly increased in keratoconus eyes (3.58 ± 2.12 mm Hg) compared to in FFK eyes (1.80 ± 3.32 mm Hg; p = 0.011). Conclusions: For eyes with keratoconus and FFK, the bIOP method is effective to adjust IOP measurements based on corneal biomechanical properties.

Analysis of leptin concentrations in oral fluids (saliva and crevicular gingival fluid) and blood in patients with chronic periodontal disease: systematic review of literature

Objective: The objective of this systematic analysis was to perform a qualitative and quantitative synthesis of the literature concerning salivary and serum leptin variations in patients with chronic periodontitis (CP) compared with healthy subjects. Saliva leptin concentration analysis could be a relevant and non-invasive biological test for the evaluation of periodontal disease in both medical and clinical trials, beyond the clinical and radiographic elements. Material and Method: Querying the PubMed and Web of Science databases identified articles that met our inclusion criteria. Quantitative analysis of the literature data was performed with the Review Manager 5.3 software. Results: The qualitative analysis included 14 articles and showed a decrease of salivary leptin (5 studies out of 5) and an increase of serum leptin (11 of 12 studies) in patients with CP compared to unaffected subjects of CP. Quantitative analysis was performed on 4 trials. For salivary leptin, we confirmed a decrease in its level in patients with CP with a standardized mean difference (SMD) of −2.27, 95% CI [−2.68, −1.86]. The difference was highly significant but we detected a very important heterogeneity in this dataset (I2 = 94%). For serum leptin, we also confirmed an increase in its rate in patients with CP with an SMD of 2.18, 95% CI [1.75, 2.61]. The difference was highly significant but the heterogeneity measured in this dataset was also too high (I2 = 95%). Conclusion: The current level of evidence was insufficient to assert an increase in serum leptin and a decrease in salivary leptin in CP patients compared to healthy controls due to a great heterogeneity of the values measured in the studies.