Zygotic Exposure to Venlafaxine Disrupts the Circadian Locomotor Activity Behaviour in Zebrafish Larvae.

The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5-day-old larvae over a 24-h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine-deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish.

Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

BACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.

Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

OBJECTIVE: To investigate the role of Ca2+/calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA). METHODS: Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2-/- mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. injections of the CaMKK2 inhibitor STO-609 (0.033 mg/kg body weight) thrice a week. Study was terminated at 8- or 12-weeks post-surgery, and knee joints processed for microcomputed tomography imaging followed by histology and immunohistochemistry. Primary articular chondrocytes were isolated from knee joints of 4-6-day-old WT and Camkk2-/- mice, and treated with 10 ng/ml interleukin-1ß (IL)-1ß for 24 or 48 h to investigate gene and protein expression. RESULTS: CaMKK2 levels and activity became elevated in articular chondrocytes following IL-1ß treatment or DMM surgery. Inhibition or absence of CaMKK2 protected against DMM-associated destruction of the cartilage, subchondral bone alterations and synovial inflammation. When challenged with IL-1ß, chondrocytes lacking CaMKK2 displayed attenuated inflammation, cartilage catabolism, and resistance to suppression of matrix synthesis. IL-1ß-treated CaMKK2-null chondrocytes displayed decreased IL-6 production, activation of signal transducer and activator of transcription 3 (Stat3) and matrix metalloproteinase 13 (MMP13), indicating a potential mechanism for the regulation of inflammatory responses in chondrocytes by CaMKK2. CONCLUSIONS: Our findings reveal a novel function for CaMKK2 in chondrocytes and highlight the potential for its inhibition as an innovative therapeutic strategy in the prevention of PTOA.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Distinct Regionalization Patterns of Cortical Morphology are Associated with Cognitive Performance Across Different Domains.

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism.

PURPOSE: To evaluate effectiveness of elamipretide in Barth syndrome (BTHS), a genetic condition of defects in TAZ, which causes abnormal cardiolipin on the inner mitochondrial membrane. METHODS: We performed a randomized, double-blind, placebo-controlled crossover trial followed by an open-label extension in BTHS to test the effect of elamipretide, a mitochondrial tetrapeptide that interacts with cardiolipin. In part 1, 12 subjects were randomized to 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm. Ten subjects continued on the open-label extension (part 2) of 40 mg per day of elamipretide, with eight subjects reaching 36 weeks. Primary endpoints were improvement on the 6-minute walk test (6MWT) and improvement on a BTHS Symptom Assessment (BTHS-SA) scale. RESULTS: In part 1 neither primary endpoint was met. At 36 weeks in part 2, there were significant improvements in 6MWT (+95.9 m, p = 0.024) and BTHS-SA (-2.1 points, p = 0.031). There were also significant improvements in secondary endpoints including knee extensor strength, patient global impression of symptoms, and some cardiac parameters. CONCLUSION: In this interventional clinical trial in BTHS, daily administration of elamipretide led to improvement in BTHS symptoms.

The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Venlafaxine deposition in the zygote disrupts the endocrine control of growth in juvenile zebrafish.

The antidepressant venlafaxine can be found at levels nearing µg/L in waterways receiving municipal wastewater effluent, exposing non-target organisms, such as fish, to this chemical. We showed previously that zygotic exposure to venlafaxine alters neurodevelopment and behaviour in zebrafish (Danio rerio) larvae. Here, we tested the hypothesis that the zygotic deposition of venlafaxine disrupts endocrine pathways related to growth in zebrafish. This was carried out by microinjecting embryos (1-4 cell stage) with either 0, 1, or 10 ng venlafaxine. Zygotic venlafaxine deposition reduced the growth of fish after 30 days post-fertilization. Specific growth rate was particularly impacted by 1 ng venlafaxine. This growth retardation corresponded with the disruption of endocrine pathways involved in growth and metabolism. Venlafaxine exposed embryos displayed reduced transcript abundance of key genes involved in anabolic hormone action. Early-life venlafaxine exposure also reduced whole-body insulin and glucose content in juveniles. Target-tissue glucose uptake measurements indicated that high venlafaxine deposition preferentially increased glucose uptake to the brain. Zygotic venlafaxine did not affect feed intake nor altered the transcript abundance of key feeding-related peptides. Taken together, zygotic venlafaxine deposition compromises zebrafish growth by disrupting multiple endocrine pathways, and this study has identified key markers for potential use in risk assessment.

Factors associated with antibiotic prescribing for adults with acute conditions: an umbrella review across primary care and a systematic review focusing on primary dental care.

INTRODUCTION: One way to slow the spread of resistant bacteria is by improved stewardship of antibiotics: using them more carefully and reducing the number of prescriptions. With an estimated 7%-10% of antibiotic prescriptions globally originating from dental practices and up to 80% prescribed unnecessarily, dentistry has an important role to play. To support the design of new stewardship interventions through knowledge transfer between contexts, this study aimed to identify factors associated with the decision to prescribe antibiotics to adults presenting with acute conditions across primary care (including dentistry). METHODS: Two reviews were undertaken: an umbrella review across primary healthcare and a systematic review in dentistry. Two authors independently selected and quality assessed the included studies. Factors were identified using an inductive thematic approach and mapped to the Theoretical Domains Framework (TDF). Comparisons between dental and other settings were explored. Registration number: PROSPERO_CRD42016037174. RESULTS: Searches identified 689 publications across primary care and 432 across dental care. Included studies (nine and seven, respectively) were assessed as of variable quality. They covered 46 countries, of which 12 were low and middle-income countries (LMICs). Across the two reviews, 30 factors were identified, with 'patient/condition characteristics', 'patient influence' and 'guidelines & information' the most frequent. Two factors were unique to dental studies: 'procedure possible' and 'treatment skills'. No factor related only to LMICs. CONCLUSIONS: A comprehensive list of factors associated with antibiotic prescribing to adults with acute conditions in primary care settings around the world has been collated and should assist theory-informed design of new context-specific stewardship interventions.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Clustering of hepatitis C virus antibody positivity within households and communities in Punjab, India.

To better understand hepatitis C virus (HCV) epidemiology in Punjab state, India, we estimated the distribution of HCV antibody positivity (anti-HCV+) using a 2013-2014 HCV household seroprevalence survey. Household anti-HCV+ clustering was investigated (a) by individual-level multivariable logistic regression, and (b) comparing the observed frequency of households with multiple anti-HCV+ persons against the expected, simulated frequency assuming anti-HCV+ persons are randomly distributed. Village/ward-level clustering was investigated similarly. We estimated household-level associations between exposures and the number of anti-HCV+ members in a household (N = 1593 households) using multivariable ordered logistic regression. Anti-HCV+ prevalence was 3.6% (95% confidence interval 3.0-4.2%). Individual-level regression (N = 5543 participants) found an odds ratio of 3.19 (2.25-4.50) for someone being anti-HCV+ if another household member was anti-HCV+. Thirty households surveyed had ⩾2 anti-HCV+ members, whereas 0/1000 (P < 0.001) simulations had ⩾30 such households. Excess village-level clustering was evident: 10 villages had ⩾6 anti-HCV+ members, occurring in 31/1000 simulations (P = 0.031). The household-level model indicated the number of household members, living in southern Punjab, lower socio-economic score, and a higher proportion having ever used opium/bhuki were associated with a household's number of anti-HCV+ members. Anti-HCV+ clusters within households and villages in Punjab, India. These data should be used to inform screening efforts.

Correction to: Sagittal balance of the spine.

The Fig. 20 is not from the study by Shiba et al., but is a courtesy from Dr. Stéphane Armand, Laboratory of Kinesiology, Geneva University Hospitals, Geneva, Switzerland.

Sagittal balance of the spine.

The static sagittal balance of the normal spine is a physiological alignment of the spine in the most efficient manner by the muscular forces. During gait, this balance is constantly thwarted by single-foot support. This analysis involves the study of parameters which are now well defined. The pelvic incidence is constant, and the sacral slope and the pelvic tilt are positional. The cervical parameters are the upper (O-C2) and lower cervical curvatures (C2-C7), the C7 slope, the spino-cranial angle and the vertical cervical offset. At the thoracic and lumbar level, they are, respectively, kyphosis and lordosis. The OD-HA (odontoid hip axis) angle is the most efficient parameter to analyse the global balance. The average values of these parameters are reported with the new 3D measurements by Le Huec et al. The relationship between these different parameters was analysed, and Roussouly proposed his classification of the different spine shape. Ageing makes it possible to show compensation mechanisms at three levels: spinal, pelvic and lower limbs. Understanding these different data allows for better planning of the surgical management of the patients. Global evaluation of the entire spine and the measurement of the aforementioned parameters allow to determine the extent of the correction to be performed during surgery. Taking these parameters into account also enables us to understand the complications involved in this type of surgery: transitional syndromes or junctional syndromes. Integration of these parameters into the study of gait is an area still under investigation. These slides can be retrieved under Electronic Supplementary Material .

Artificial Intelligence-Assisted Auscultation of Heart Murmurs: Validation by Virtual Clinical Trial.

Artificial intelligence (AI) has potential to improve the accuracy of screening for valvular and congenital heart disease by auscultation. However, despite recent advances in signal processing and classification algorithms focused on heart sounds, clinical acceptance of this technology has been limited, in part due to lack of objective performance data. We hypothesized that a heart murmur detection algorithm could be quantitatively and objectively evaluated by virtual clinical trial. All cases from the Johns Hopkins Cardiac Auscultatory Recording Database (CARD) with either a pathologic murmur, an innocent murmur or no murmur were selected. The test algorithm, developed independently of CARD, analyzed each recording using an automated batch processing protocol. 3180 heart sound recordings from 603 outpatient visits were selected from CARD. Algorithm estimation of heart rate was similar to gold standard. Sensitivity and specificity for detection of pathologic cases were 93% (CI 90-95%) and 81% (CI 75-85%), respectively, with accuracy 88% (CI 85-91%). Performance varied according to algorithm certainty measure, age of patient, heart rate, murmur intensity, location of recording on the chest and pathologic diagnosis. This is the first reported comprehensive and objective evaluation of an AI-based murmur detection algorithm to our knowledge. The test algorithm performed well in this virtual clinical trial. This strategy can be used to efficiently compare performance of other algorithms against the same dataset and improve understanding of the potential clinical usefulness of AI-assisted auscultation.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Modelling of focused ion beam induced increases in sample temperature: a case study of heat damage in biological samples.

Ion beam induced heat damage in soft materials and biological samples is not yet well understood in Focused Ion Beam systems (FIBs). The work presented here discusses the physics behind the ion beam - sample interactions and the effects which lead to increases in sample temperature and potential heat damage. A model by which heat damage can be estimated and which allows parameters to be determined that reduce/prevent heat damage was derived from Fourier's law of heat transfer and compared to finite element simulations, numerical modelling results and experiments. The results suggests that ion beam induced heat damage can be prevented/minimised by reducing the ion beam current (local dose rate), decreasing the beam overlap (reduced local ion dose) and by introducing a blur (increased surface cross-section area, reduced local dose) while sputtering, patterning or imaging soft material and nonresin-embedded biological samples using FIBs. LAY DESCRIPTION: FIB/SEMs, which combine a scanning electron microscope with a focused ion beam in a single device, have found increasing interest biological research. The device allows to cut samples at precisely selected areas and reveal sub surface information as well as preparing transmission electron microscope samples from bulk materials. Preparing biological samples has proven to be challenging due to the induced heat damage. This work explores the physics behind the sample cutting and proposes a model and a method, based on physical principles which allows the user to estimate the induced heat during the cutting process and to select cutting parameters which avoid heat damage in the sample.

Analysis of cervical sagittal alignment variations after lumbar pedicle subtraction osteotomy for severe imbalance: study of 59 cases.

OBJECTIVE: To evaluate postoperative changes within the cervical alignment following surgical lumbar correction by pedicle subtraction osteotomy (PSO) in patients affected with sagittal global malalignment disease. METHODS: This was a monocentric, radiographic, and prospective study. 79 patients, who underwent sagittal correction by PSO, performed an EOS imaging pre- and postoperatively between January 2008 and December 2013 at the University Hospital of Bordeaux. Inclusion criteria were a performed pre- and postoperative EOS imaging and a preoperative C7SVA > 5 cm. Were excluded patients who did not allow EOS with a viewable cervical spine due to hyperkyphosis. The study involved the analysis of pelvic, lumbar, thoracic, cervical, and cranial parameters before and after the surgery. RESULTS: 59 patients met the criteria. Mean follow-up was 38 months. The lumbar PSO significantly improved sagittal alignment including L1S1 lordosis, T1T12 kyphosis, and C7SVA (p < 0.001). We did not reported a significant change within cervical parameters after PSO (C2C7 lordosis 22.7°-21.5° p = 0.64, C1C7 lordosis 50.6°-48.8° p = 0.56, C1C2 angle 28.2°-27.9° p = 0.82, C7 slope stayed constant 32.3°-30.5° p = 0.47, OC2 angle 15.54°-15.56° p = 0.99). However, cranial slope decreased significantly (p < 0.05). We did not find correlation between lumbar lordosis and cervical lordosis variations (R = 0.265). Cervical lordosis was highly correlated with the C7 slope (R = 0.597) and with the Spino Cranial Angle (R = - 0.867). CONCLUSION: Reciprocal changes in cervical spine after PSO are difficult to approach. Maintaining a horizontal gaze involves locoregional mechanisms of compensation adapting to the slope of C7. The cranial system by decreasing the cranial slope allows the gaze alignment and is the first compensation mechanism to get involved after a loss of lumbar lordosis. Restoring optimal C7SVA is necessary to prevent the development of secondary cervical painful symptomatology when the cranial compensation is outdated.

Which parameters are relevant in sagittal balance analysis of the cervical spine? A literature review.

INTRODUCTION: Cervical spine is part of the spine with the most mobility in the sagittal plane. It is important for surgeons to have reliable, simple and reproducible parameters to analyse the cervical. MATERIAL AND METHOD: This study is a systematic review and a critique of current parameters to help improve the study of cervical spinal balance. We conducted a systematic search of PUBMED/MEDLINE for literature published since January 2014. Only studies written in English and containing abstracts were considered for inclusion. The search performed was: «C7 slope¼ OR «T1 slope¼ OR «C2C7 offset¼ OR «C2C7 lordosis¼ OR «cervical SVA (sagittal vertical axis)¼ OR «TIA (thoracic inlet angle)¼ (Lee et al., J Spinal Disord Tech 25(2):E41-E47, 2012) OR «SCA (spino-cranial angle)¼. Exclusion criteria were purely post-operative and cadaveric analysis, studies performed with CT scan or MRI, studies on adolescent idiopathic scoliosis, traumatology studies and no standing analysis of the cervical spine. Relevance was confirmed by investigators if cervical parameters was a major criteria of the study. RESULTS: 138 articles were found by the electronic search. After complete evaluation 20 articles were selected. The large majority of papers used the same parameters C2_C7 lordosis, C2-C7 SVA, T1 slope or C7 slope and T1 slope/cervical lordosis mismatch. Janusz reported a new parameter using a retrospective cohort of patient with cervical radiculopathy: the TIA (thoracic inlet angle). Le Huec reported an other new parameter based on a prospective study of asymptomatic volunteer: the spino-cranial angle (SCA). This parameter is highly correlated with the C7 slope and the cervical lordosis. Other studies reported parameters that are more global balance analysis including the cervical spine than cervical spine balance itself. CONCLUSION: The most important parameters to analyse the cervical sagittal balance according to the literature available today for good clinical outcomes are the following: C7 or T1 slope, average value 20°, must not be higher than 40°. cSVA must not be less than 40°C (mean value 20 mm). SCA (spine cranial angle) must stay in a norm (83° ± 9°). Future studies should focus on those three parameters to analyse and compare pre and post op data and to correlate the results with the quality of life improvement.