Magnetotactic bacteria produce chains of nanoscopic iron minerals used for navigation, which can be preserved over geological timescales in the form of magnetofossils. Micrometer-sized magnetite crystals with unusual shapes suggesting a biologically controlled mineralization have been found in the geological record and termed giant magnetofossils. The biological origin and function of giant magnetofossils remains unclear, due to the lack of modern analogues to giant magnetofossils. Using distinctive Ptychographic nanotomography data of Precambrian (1.88 Ga) rocks, we recovered the morphology of micrometric cuboid grains of iron oxides embedded in an organic filamentous fossil to construct synthetic magnetosomes. Their morphology is different from that of previously found giant magnetofossils, but their occurrence in filamentous microfossils and micromagnetic simulations support the hypothesis that they could have functioned as a navigation aid, akin to modern magnetosomes.

OBJECTIVE: Primordial odontogenic tumor is a rare odontogenic tumor reported for the first time in 2014. It was included in the latest edition of World Health Organization classification of Head and Neck Tumors as a new benign mixed epithelial-mesenchymal neoplasm. To date, 26 cases has been reported in literature. The aim of this study was to determine the possible presence of primordial odontogenic tumor in the previously diagnosed cases with myxoid stroma.
METHODS: This study was a retrospective descriptive study that was concluded in Oral and Maxillofacial Pathology Department, School of Dentistry, Tehran University of Medical Sciences. We reviewed all 19,380 cases from 19,66 to find the lesions with myxoid stroma which were in differential diagnosis with primordial odontogenic tumor. These cases should be associated with an impacted or unerupted tooth and belong to the patients under 20 years old.
RESULTS: We find 503 pericoronal lesions with myxoid stroma. Three cases were isolated after recut and reevaluation for finding fulfill histologic features. After immunohistochemical analysis, we find a new case of developing primordial odontogenic tumor associated with odontoma.
CONCLUSIONS: Primordial odontogenic tumor a recently described odontogenic tumor has a well-defined clinicopathological and immunohistochemical profile and should be differentiated from the others pericoronal lesions. It is the first time that this archival review has been done to find probable cases of primordial odontogenic tumor.

Primordial odontogenic tumour (POT) is a newly described benign mixed odontogenic neoplasm that has been included in the World Health Organization classification 2017. Only 19 cases that conform to the clinico-pathologic criteria for diagnosis have been reported worldwide. We present the 20th case of POT reported worldwide and is only the third case to be reported from India. The need for considering POT as a possible diagnosis in lesions affecting posterior mandible in patients below 10 years, the need for clinicians and pathologists to be aware of this entity and the need to draw more specific conclusions on the diagnostic criteria of POT make it necessary to report every single case of this entity from different parts of the world. Along with the case report in a 3-year-old child patient, we also present here a summary of the cases reported till date and the review of literature.

Primordial odontogenic tumor (POT) is a rare mixed odontogenic tumor composed of primitive ectomesenchyme similar to the dental papilla. The outer surface consists of columnar/cuboidal odontogenic epithelium similar to the inner enamel epithelium, and there is no hard tissue formation. Until now, 27 cases have been reported in the English literature. This article describes the clinicopathological characteristics of one case of POT, representing the oldest patient (aged 26 years) reported to date.

Environmental factors including household crowding and inadequate washing facilities underpin recurrent streptococcal infections in childhood that cause acute rheumatic fever (ARF) and subsequent rheumatic heart disease (RHD). No community-based \'primordial\'-level interventions to reduce streptococcal infection and ARF rates have been reported from Australia previously. We conducted a study at three Australian Aboriginal communities aiming to reduce infections including skin sores and sore throats, usually caused by Group A Streptococci, and ARF. Data were collected for primary care diagnoses consistent with likely or potential streptococcal infection, relating to ARF or RHD or related to environmental living conditions. Rates of these diagnoses during a one-year Baseline Phase were compared with a three-year Activity Phase. Participants were children or adults receiving penicillin prophylaxis for ARF. Aboriginal community members were trained and employed to share knowledge about ARF prevention, support reporting and repairs of faulty health-hardware including showers and provide healthcare navigation for families focusing on skin sores, sore throat and ARF. We hypothesized that infection-related diagnoses would increase through greater recognition, then decrease. We enrolled 29 participants and their families. Overall infection-related diagnosis rates increased from Baseline (mean rate per-person-year 1.69 [95% CI 1.10-2.28]) to Year One (2.12 [95% CI 1.17-3.07]) then decreased (Year Three: 0.72 [95% CI 0.29-1.15]) but this was not statistically significant (p = 0.064). Annual numbers of first-known ARF decreased, but numbers were small: there were six cases of first-known ARF during Baseline, then five, 1, 0 over the next three years respectively. There was a relationship between household occupancy and numbers (p = 0.018), but not rates (p = 0.447) of infections. This first Australian ARF primordial prevention study provides a feasible model with encouraging findings.

Physician burnout, as described in North America, is a multidimensional work-related syndrome that includes emotional exhaustion, depersonalization, and a low sense of accomplishment from work. More than 50% of physicians were reporting symptoms of burnout prior to the COVID-19 pandemic. This silent epidemic of burnout is bound to become less silent as the pandemic continues. Lifestyle medicine is an evidence-based discipline that describes how daily habits and health practices can affect overall health and well-being of individuals. Lifestyle Medicine can potentially play a significant role in preventing and ameliorating physician burnout. This article explores the burnout process, including the historical context, international definitions, symptoms, and imprecision of the clinical diagnosis. The systemic etiological issues are discussed, and the psychological underpinnings are explored, including physicians\' personal vulnerabilities contributing to burnout. The stress response and lifestyle medicine\'s role in healthy coping are described. A prevention model for risk factor reduction is proposed, focusing on primordial, primary, secondary, and tertiary prevention. Lifestyle medicine clinicians\' role in prevention, treatment, and advocacy to ameliorate the potential for burnout is discussed along with specific recommendations.

What is the impact of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, alone or in combination with chemotherapy on the ovary in mice?
Olaparib treatment, when administered alone, depletes primordial follicle oocytes, but olaparib does not exacerbate chemotherapy-mediated ovarian follicle loss in mice.
The ovary contains a finite number of oocytes stored within primordial follicles, which give rise to all mature ovulatory oocytes. Unfortunately, they are highly sensitive to exogenous DNA damaging insults, such as cytotoxic cancer treatments. Members of the PARP family of enzymes are central to the repair of single-strand DNA breaks. PARP inhibitors have shown promising clinical efficacy in reducing tumour burden, by blocking DNA repair capacity. Olaparib is a PARP1/2 inhibitor recently FDA-approved for treatment of BRCA1 and BRCA2 mutation carriers with metastatic breast cancer. It is currently being investigated as an adjunct to standard treatment at an earlier stage, potentially curable, BRCA1- and BRCA2-associated breast cancer which affects reproductive age women. Despite this, there is no preclinical or clinical information regarding the potential impacts of olaparib on the ovary or on female fertility. Unfortunately, it may be many years before clinical data on fertility outcomes for women treated with PARP inhibitors becomes available, highlighting the importance of rigorous preclinical research using animal models to establish the potential for new cancer therapies to affect the ovary in humans. We aimed to comprehensively determine the impact of olaparib alone, or following chemotherapy, on the ovary in mice.
On Day 0, mice (n = 5/treatment group) were administered a single intraperitoneal dose of cyclophosphamide (75 mg/kg/body weight), doxorubicin (10 mg/kg), carboplatin (80 mg/kg), paclitaxel (7.5 mg/kg) or vehicle control. From Days 1 to 28, mice were administered subcutaneous olaparib (50 mg/kg) or vehicle control. This regimen is proven to reduce tumour burden in preclinical mouse studies and is also physiologically relevant for women.
Adult female wild-type C57BL6/J mice at peak fertility (8 weeks) were administered a single intraperitoneal dose of chemotherapy, or vehicle, then either subcutaneous olaparib or vehicle for 28 days. Vaginal smears were performed on each animal for 14 consecutive days from Days 15 to 28 to monitor oestrous cycling. At 24 h after final treatment, ovaries were harvested for follicle enumeration and immunohistochemical analysis of primordial follicle remnants (FOXL2 expressing granulosa cells), DNA damage (γH2AX) and analysis of apoptosis by TUNEL assay. Serum was collected to measure circulating anti-Müllerian hormone (AMH) concentrations by ELISA.
Olaparib significantly depleted primordial follicles by 36% compared to the control (P < 0.05) but had no impact on other follicle classes, serum AMH, corpora lutea number (indicative of ovulation) or oestrous cycling. Primordial follicle remnants were rarely detected in control ovaries but were significantly elevated in ovaries from mice treated with olaparib alone (P < 0.05). Similarly, DNA damage denoted by γH2AX foci was completely undetectable in primordial follicles of control animals but was observed in ∼10% of surviving primordial follicle oocytes in mice treated with olaparib alone. These observations suggest that functional PARPs are essential for primordial follicle oocyte maintenance and survival. Olaparib did not exacerbate chemotherapy-mediated follicle depletion in the wild-type mouse ovary.
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This study was performed in mice, so the findings may not translate to women and further studies utilizing human ovarian tissue and sera samples should be performed in the future. Only one long-term time point was analysed, therefore olaparib-mediated follicle damage should be assessed at more immediate time points in the future to support our mechanistic findings.
Olaparib dramatically depleted primordial follicles and this could be attributed to loss of intrinsic PARP-mediated DNA repair mechanisms. Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility. Notably, the extent of follicle depletion might be enhanced in BRCA1 and BRCA2 mutation carriers, and this is the subject of current investigations. Together, our data suggest that fertility preservation options should be considered for young women prior to olaparib treatment, and that human studies of this issue should be prioritized.
This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the National Health and Medical Research Council (NHMRC); (K.J.H. #1050130) (A.L.W. #1120300). K.A.P. is a National Breast Cancer Foundation Fellow (Australia-PRAC-17-004). K.A.P. is the Breast Cancer Trials (Australia) Study Chair for the OlympiA clinical trial sponsored by AstraZeneca, the manufacturer of olaparib. All other authors declare no competing financial or other interests.

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Maintenance and activation of the limited supply of primordial follicles in the ovary are important determinants of reproductive lifespan. Currently, the molecular programme that maintains the primordial phenotype and the early events associated with follicle activation are not well defined. Here, we have systematically analysed these events using microscopy and detailed image analysis. Using the immature mouse ovary as a model, we demonstrate that the onset of granulosa cell (GC) proliferation results in increased packing density on the oocyte surface and consequent GC cuboidalization. These events precede oocyte growth and nuclear translocation of FOXO3a, a transcription factor important in follicle activation. Immunolabelling of the TGFβ signalling mediators and transcription factors SMAD2/3 revealed a striking expression pattern specific to GCs of small follicles. SMAD2/3 were expressed in the nuclei of primordial GCs but were mostly excluded in early growing follicles. In activated follicles, GC nuclei lacking SMAD2/3 generally expressed Ki67. These findings suggest that the first phenotypic changes during follicle activation are observed in GCs, and that TGFβ signalling is fundamental for regulating GC arrest and the onset of proliferation.

Introduction: Primordial odontogenic tumors are a rare recently described mixed odontogenic tumor composed histopathologically of dental papilla like tissue and enamel organ like tissue. Only nine cases have been documented worldwide and we are reporting the tenth case which is from Egypt. Clinical finding: A 2-year-old Egyptian boy that presented with an asymptomatic swelling of the mandible which appeared with multilocular radiolucency associated with an impacted developing tooth on a computerized tomography (CT) scan. Diagnoses, interventions, and outcomes: The lesion was excised and diagnosed as a primordial odontogenic tumor. The patient was followed up for two years with no recurrence. Conclusion: Differentiation of primordial odontogenic tumors from other odontogenic tumors, which resemble it histopathologically is crucial to avoid unnecessary aggressive treatment.