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PurposeAdolescent idiopathic scoliosis (AIS) is believed to be caused by genetic, neurological, osseous growth anomalies, histological variables including muscle fiber percentage and core structure changes, metabolic and hormonal dysfunction, vestibular dysfunction, and platelet microarchitecture. The objective of this study was to contribute to the determination of the cause of AIS by analyzing the changes in pineal gland volume in AIS cases.MethodsStudy (AIS) and control group were each comprised of 26 patients who met the inclusion requirements. Scoliosis radiograph and MRI of the pineal glands were used for radiological examinations. The distribution of age, gender, Risser grading for skeletal radiological development, and sexual maturation according to Tanner categorization were uniform and statistically insignificant between groups.ResultsWhen the pineal gland volumes of the cases were evaluated according to age, the AIS group was found to have significantly reduced pineal gland volumes in all age groups. The pineal gland volume was found to be 38.1% lower in the AIS group compared to the control group (p˂0.001). In the AIS group, patients aged 13 years had the lowest pineal gland volume (77.2 ± 13.86 mm3), while patients aged 15 years had the highest volume (97.9 ± 16.47 mm3).ConclusionChanges in pineal gland volume support the role of the pineal gland in the etiopathogenesis of AIS.

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin’s synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans. Graphical Abstract

ObjectivesTo report the results of an international patient-reported survey that adds to the growing body of evidence surrounding the role of surgery in the management of a subset of patients with non-hydrocephalic symptomatic pineal cyst.DesignAn international web-based survey of health outcomes in patients with nhSPC.SubjectsAll survey participants who self-reported a diagnosis of symptomatic pineal cyst without hydrocephalus after radiological imaging.MethodsThe survey was developed in collaboration with the patient group Pineal Cyst UK. It was publicised and distributed via several online platforms and social media. Data collected included demographics, cyst size, symptom frequency and severity, number of appointments with healthcare professionals, treatment options trialled, and whether patients underwent surgery.Results543 participants (mean age 38.6 years, range 1–83) were included in the analysis, of which 82 (mean age 38.9 years, range 16–72) had undergone cyst resection. After a median period of 18.3 months between date of surgery and date of questionnaire completion, 72 (90%) of the surgical cohort reported overall improvement, and all symptoms improved overall, whereas no symptoms improved overall in the non-surgical cohort. Of the non-surgical cohort (n = 461), 269 participants received some form of conservative treatment, of whom 194 (72.1%) did not experience symptom improvement on any treatment offered.ConclusionsA cohort of patients with nhSPC who participated in this international survey reports substantial and durable improvement in symptom severity and quality of life after pineal cyst resection.

PurposeMedulloblastoma, the most common primary pediatric malignant brain tumor, originates in the posterior fossa of the brain. Pineoblastoma, which originates within the pineal gland, is a rarer malignancy that also presents in the pediatric population. Medulloblastoma and pineoblastoma exhibit overlapping clinical features and have similar histopathological characteristics. Histopathological similarities confound rapid diagnoses of these two tumor types. We have conducted a pilot feasibility study analyzing the molecular profile of archived frozen human tumor specimens using mass spectrometry imaging (MSI) to identify potential biomarkers capable of classifying and distinguishing between medulloblastoma and pineoblastoma.MethodsWe performed matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry imaging on eight medulloblastoma biopsy specimens and three pineoblastoma biopsy specimens. Multivariate statistical analyses were performed on the MSI dataset to generate classifiers that distinguish the two tumor types. Lastly, the molecules that were discriminative of tumor type were queried against the Lipid Maps database and identified.ResultsIn this pilot study we show that medulloblastoma and pineoblastoma can be discriminated using molecular profiles determined by MSI. The highest-ranking discriminating classifiers of medulloblastoma and pineoblastoma were glycerophosphoglycerols and sphingolipids, respectively.ConclusionWe demonstrate proof-of-concept that medulloblastoma and pineoblastoma can be rapidly distinguished by using MSI lipid profiles. We identified biomarker candidates capable of distinguishing these two histopathologically similar tumor types. This work expands the current molecular knowledge of medulloblastoma and pineoblastoma by characterizing their lipidomic profiles, which may be useful for developing novel diagnostic, prognostic and therapeutic strategies.

Background and Objectives: The pineal gland is a neuroendocrine structure whose function can be disrupted in patients with malignancies. This study examines the differences in pineal gland volume between oncology patients and healthy controls, as well as the relationship between volume and the duration of chemotherapy. Materials and Methods: A retrospective study included 400 participants, divided into two groups: 200 oncology patients and 200 healthy controls. The pineal gland volume was measured using MRI scans, utilizing T1-sagittal, T2-coronal/axial sections, and post-contrast 3D T1W MPRAGE tomograms. The volume was calculated based on the ellipse approximation formula: V = (L × H × W)/2. The study analyzed the relationships between pineal gland volume and factors such as age, sex, primary tumor origin, and the duration of chemotherapy. Results: The pineal gland volume was significantly smaller in oncology patients in comparison with the healthy controls (p < 0.001). The average volume in oncology patients was 32.41 ± 16.79 mm3, whereas in healthy controls, it was 59.26 ± 29.99 mm3. A significantly smaller pineal gland volume was observed in patients with malignancies, regardless of sex, with no notable differences between groups. Age also did not significantly influence gland volume (p > 0.05). The primary tumor site did not significantly influence gland volume (p > 0.05). A moderate positive correlation was observed between the duration of chemotherapy and pineal gland volume (ρ = 0.322; p = 0.007). Conclusions: The pineal gland showed reduced volume in oncology patients compared to controls. The observed positive correlation with chemotherapy duration should be interpreted cautiously and may reflect survivorship bias rather than direct treatment effects.

The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

BackgroundOur aim was to determine whether the Apparent Diffusion Coefficient is able to predict the presence of a symptomatic pineal cyst by detecting cerebral edema.MethodsWe retrospectively analyzed MRIs of 45 patients with pineal cysts before and after resection and 51 patients without pineal cysts, comparing ADC values of thalamus, central, periventricular and subcortical white matter. Furthermore we evaluated cyst size and morphology and analyzed its correlation to ADC values in corresponding patients.ResultsDifferences between patients with symptomatic pineal cyst and control group were not significant (p = 0.200 – 0.968). ADC ratios did not change significantly after resection of the cyst (p = 0.575 – 0.862). Cyst size showed no significant correlation to ADC ratios (p = 0.071 – 0.918). Raw data analyses revealed more significance, especially periventricularly and in central white matter, which resulted in significant interhemispheric differences in ADC ratios in both subgroups (p < 0.001 and p = 0.031). MRI of 1.5T showed consistently higher values than 3T but mostly insignificant.ConclusionOur analysis revealed no evidence that pineal cysts lead to intracerebral edema caused by venous compression. Since variability was higher than the differences seen, ADC sequences do not appear to be an appropriate diagnostic tool for symptomatic pineal cysts.

The pineal gland secretes melatonin principally at night. Regulated by norepinephrine released from sympathetic nerve terminals, adrenergic receptors on pinealocytes activate aralkylamine N-acetyltransferase that converts 5-hydroxytryptamine (5-HT, serotonin) to N-acetylserotonin, the precursor of melatonin. Previous studies from our group and others reveal significant constitutive secretion of 5-HT from pinealocytes. Here, using mass spectrometry, we demonstrated that the 5-HT is secreted primarily via a decynium-22–sensitive equilibrative plasma membrane monoamine transporter instead of by typical exocytotic quantal secretion. Activation of the endogenous 5-HT receptors on pinealocytes evoked an intracellular Ca2+ rise that was blocked by RS-102221, an antagonist of 5-HT2C receptors. Applied 5-HT did not evoke melatonin secretion by itself, but it did potentiate melatonin secretion evoked by submaximal norepinephrine. In addition, RS-102221 reduced the norepinephrine-induced melatonin secretion in strips of pineal gland, even when no exogenous 5-HT was added, suggesting that the 5-HT that is constitutively released from pinealocytes accumulates enough in the tissue to act as an autocrine feedback signal sensitizing melatonin release.

ABSTRACT The pituitary and pineal glands are two small yet critical brain structures that help to modulate the human endocrine system. Unfortunately, very little research has been devoted to segmenting the pineal gland, and existing methods for pituitary segmentation focus only on the entire gland without distinguishing between its two lobes. To fill this gap, this work presents the first deep‐learning‐based tool for segmentation of both the pineal and pituitary glands in T1‐weighted MRI. A five‐fold cross‐validation study was conducted on a manually labeled training dataset and produced segmentations with accuracy comparable to similar methods for segmenting other small brain structures. Model performance was then tested in three publicly available datasets using a total of n = 816 subjects, the results of which were both highly reproducible and robust to differences in MRI scanners and acquisition protocols. Finally, an analysis was performed to identify group differences related to sex and the diagnosis of schizophrenia and showed that volumes measured from the output segmentations were effective at discerning sex‐ and disease case‐related differences in the pituitary and pineal glands. This work presents a deep‐learning‐based tool for automatic segmentation of the pituitary and pineal glands. It has two novel aspects: it considers the anterior and posterior lobes as separate labels rather than a single, combined structure, and it is also the first deep‐learning protocol for pineal gland segmentation.