Identification of the Remains of an Adult Using DNA from Their Deciduous Teeth as a Reference Sample.

In many forensic cases, the identification of human remains is performed by comparing their genetic profile with profiles from reference samples of relatives, usually the parents. Here, we report, for the first time, the identification of the remains of an adult using DNA from the person's deciduous teeth as a reference sample. Fragments of a skeletonized and burned body were found, and a short tandem repeat (STR) profile was obtained. A woman looking for her missing son went to the authorities. When the DNA profile of the woman was compared to a database, a positive match suggested a first-degree kinship with the person to whom the remains belonged. The woman had kept three deciduous molars from her son for more than thirty years. DNA typing of dental pulp was performed. The genetic profiles obtained from the molars and those from the remains coincided in all alleles. The random match probability was 1 in 2.70 × 1021. Thus, the remains were fully identified. In the routine identification of human remains, ambiguous STR results may occur due to the presence of null alleles or other mutational events. In addition, erroneous results can be produced by false matches with close family members or even with people who are completely unrelated to the victim, such that, in some cases, a probability of paternity greater than 99.99% does not necessarily indicate biological paternity. Whenever possible, it is preferable to use reference samples from the putative victim as a source of DNA for identification.

The Convoluted Tubules of the Nephron Must Be Considered Elliptical, and Not Circular, in Stereological Studies of the Kidney.

INTRODUCTION: The diameter and area of the proximal convoluted tubule (PCT) and the distal convoluted tubule (DCT) are of the main parameters analyzed in stereological studies of the kidney. However, there is no consensus about if the PCT and DCT should be considered circular or elliptical in shape. OBJECTIVE: To analyze if there are significant differences in the diameter and area of the PCT and DCT, depending on whether they are considered circular or elliptical. METHODS: Paraffin-embedded sections of kidneys from CD1 mice were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to image analysis software. A short diameter (d) and a long diameter (D) were measured in both PCT and DCT. A small circular area (SCA), a large circular area (LCA), and an elliptical area (EA) were calculated with mathematical formulas that incorporate d and D values, while a program area (PA) was provided by the software. RESULTS: There was a significant difference between d and D in both PCT (F = 1.354, Sig = 0.000) and DCT (F = 4.989, Sig = 0.000). Also, there were significant differences in the tubular areas in both PCT (F = 34.843, Sig = 0.000) and DCT (F = 22.390, Sig = 0.000); circular areas were different from elliptical areas (SCA and LCA vs. EA and PA). CONCLUSION: The convoluted tubules of the nephron must not be considered circular, but rather elliptical; care should be taken every time the tubules are analyzed in stereological studies of the kidney, especially when evaluating their diameters and areas.

Peroxisomicine A1, a potential antineoplastic agent, causes micropexophagy in addition to macropexophagy.

Peroxisomicine A1 (PA1) is a potential antineoplastic agent with high and selective toxicity toward peroxisomes of tumor cells. Pexophagy is a selective autophagy process that degrades damaged peroxisomes; this process has been studied mainly in methylotrophic yeasts. There are two main modes of pexophagy in yeast: macropexophagy and micropexophagy. Previous studies showed that peroxisomes damaged by a prolonged exposition to PA1 are eliminated by macropexophagy. In this work, Candida boidinii was grown in methanol-containing media, and PA1 was added to the cultures at 2 µg/mL after they reached the mid-exponential growth phase. Samples were taken at 5, 10, 15, 20, and 25 min after the addition of PA1 and processed for ultrastructural analysis. Typical morphological characteristics of micropexophagy were observed: the direct engulfment of peroxisomes by the vacuolar membrane and the presence of the micropexophagic membrane apparatus (MIPA), which mediates the fusion between the opposing tips of the vacuole to complete sequestration of peroxisomes from the cytosol. In conclusion, here we report that, in addition to macropexophagy, peroxisomes damaged by PA1 can be eliminated by micropexophagy. This information is useful to deepen the knowledge of the mechanism of action of PA1 and of that of pexophagy per se.

Toxicity and Anticancer Potential of Karwinskia: A Review.

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the toxicity of the fruit of Karwinskia plants when ingested (accidentally or experimentally), as well as the toxicity of its isolated compounds. Additionally, we analyze the probable antineoplastic effect of T514. Toxins cause damage mainly to nervous system, liver, lung, and kidney. The pathophysiological mechanism has not been fully understood but includes metabolic and structural alterations that can lead cells to apoptosis or necrosis. T514 has shown selective toxicity in vitro against human cancer cells. T514 causes selective and irreversible damage to peroxisomes; for this reason, it was renamed peroxisomicine A1 (PA1). Since a significant number of malignant cell types contain fewer peroxisomes than normal cells, tumor cells would be more easily destroyed by PA1 than healthy cells. Inhibition of topoisomerase II has also been suggested to play a role in the effect of PA1 on malignant cells. More research is needed, but the evidence obtained so far indicates that PA1 could be an effective anticancer agent.

Anterior sacral meningocele presenting as intracystic bleeding.

PURPOSE: To report a case of anterior sacral meningocele with intralesional bleeding secondary to sacrococcygeal trauma. Likewise, there is a discussion about the physiopathology and the surgical approach to these types of lesions. METHODS: A 43-year-old man diagnosed with Marfan syndrome suffered sacrococcygeal trauma. He was admitted to the emergency room due to symptoms of headache, nausea, and lower limb subjective weakness. CT and MRI showed a large retroperitoneal mass with hemorrhagic content close to the sacrum. Likewise, the MRI showed an image compatible with subarachnoid hemorrhage in the thoracic spinal area, cerebral convexity, and the basal cisterns. The patient went into surgery for an anterior abdominal approach in the midline to reduce the content of the lesion, and subsequently, in the same act, a posterior approach was done with an S1-S2 laminectomy and obliteration of the pedicle. Postoperative MRI 5 months later showed resolution of the ASM. RESULTS: Anterior sacral meningocele is characterized by herniation of the dura mater and the arachnoid mater outside the spinal canal through a defect of the sacrum. We add the risk of bleeding after trauma-never seen in the literature-as one of the possible inherent complications of this lesion. CONCLUSIONS: This report highlights a complication never seen in the literature of a relatively rare condition. In our case, the combined approach was effective for both clinical control and lesion regression.

[Trigeminal neuralgia secondary to petrous endostosis]. / Neuralgia del trigémino secundaria a endostosis del hueso temporal.

Arterial neurovascular compression is hypothesised to be the main cause of primary trigeminal neuralgia. Although it is the most common cause, other pathologies, such as tumours in the cerebellopontine angle, can cause trigeminal pain. We report a case of a 44-year-old female patient with right trigeminal neuralgia without satisfactory response to medical treatment. Cerebral MRI showed no structural injuries. During microvascular decompression of the trigeminal nerve, endostosis of the internal aspect of the petrous bone was found to compress the trigeminal nerve. The pain disappeared completely in the early postsurgical period, after the complete drilling of the endostosis and microvascular decompression. The patient remains asymptomatic one year later. Endostosis of the petrous bone is a rare cause of trigeminal neuralgia. A proper review of preoperative studies would enable the definitive surgical approach to be optimised.

Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process.

PURPOSE: Aging is associated with changes in the lung that leads to a decrease in its function. Alterations in structure and function in the small airways are well recognized in chronic lung diseases. The aim of this study was the assessment of cell turnover in the bronchiolar epithelium of mouse through the normal aging process. METHODS: Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Proliferating cell nuclear antigen was examined by immunohistochemistry. Apoptosis was analyzed by in situ end-labeling of fragmented DNA. Epithelial dimensions were analyzed by morphometry. RESULTS: The 2-month-old mice showed significantly higher number of proliferating cells when compared with mice at all other age groups. The number of apoptotic cells in mice at 24 months of age was significantly greater than in mice at all other age groups. Thus, the number of epithelial cells decreased as the age of the subject increased. We also found reductions in both area and height of the bronchiolar epithelium in mice at 18 and 24 months of age. CONCLUSIONS: We found a decrease in the total number of epithelial cells in the aged mice, which was accompanied by a thinning of the epithelium. These changes reflect a dysregulated tissue regeneration process in the bronchiolar epithelium that might predispose to respiratory diseases in elderly subjects.

Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium.

Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow-derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases.

[Elusive thoracic spine tumour. Report of an exceptional case and literature review]. / Tumor elusivo dorsal. Presentación de un caso excepcional y revisión de la bibliografía.

Elusive tumours in the spine, most of them schwannomas of the cauda equina, have been reported very rarely. We present the case of a woman with a preoperative radiological diagnosis of schwannoma at D10 level in whom a laminectomy was performed to remove the tumour. Although the laminectomy was correctly positioned, there was no tumour upon opening the dura and the laminectomy had to be extended cephalad to find and remove the tumour. Mobile intradural extramedullary spinal tumours, the so-called «elusive tumours¼, occur very rarely, and it is exceptional when they are located in the thoracic spine. Knowing preoperatively which tumour is going to behave in this way is almost impossible. However, in the reported cases there are common features such as symptoms changing with different body positions, small tumour size and weak attachment to nearby structures. Neurosurgeons must be able to resolve this situation when confronted with a negative correctly-positioned laminectomy.

p53 E3 ubiquitin protein ligase homolog regulates p53 in vivo in the adult mouse eye lens.

PURPOSE: p53 is a transcription factor that plays an important role in preventing cancer development. p53 participates in relevant aspects of cell biology, including apoptosis and cell cycle control and must be strictly regulated to maintain normal tissue homeostasis. p53 E3 ubiquitin protein ligase homolog (Mdm2) is an important negative regulator of p53. The purpose of this study was to determine if Mdm2 regulates p53 in vivo in the adult lens. METHODS: We analyzed mice expressing human p53 transgene (Tgp53) selectively in the lens in the presence or absence of Mdm2. Mice with the required genotypes were obtained by crossing transgenic, mdm2 (+/-), and p53 (-/-) mice. Eye phenotype and lens histology and ultrastructure were analyzed in adult mice. RESULTS: In a wild-type genetic background (mdm2 (+/+)), lens damage and microphthalmia were observed only in mice homozygous for Tgp53 ((t/t)). However, in an mdm2 null background, just one allele of Tgp53 (mdm2 (-/-)/Tgp53 (t/0) mice) was sufficient to cause lens damage and microphthalmia. Furthermore, Mdm2 in only one allele was sufficient to rescue these deleterious effects, since the mdm2 (+/-)/Tgp53 (t/0) mice had eye size and lens morphology similar to the control mice. CONCLUSIONS: Mdm2 regulates p53 in the adult lens in vivo. This information may have relevance for analyzing normal and pathological conditions of the lens, and designing cancer therapies targeting Mdm2-p53 interaction.

Evidence of chondrocyte turnover in lung cartilage, with the probable participation of nestin-positive cells.

Healthy adult cartilage is thought to have little or no capacity to renewal, and cell turnover has not been reported in lung cartilage. We report that chondrocyte turnover occurs in lung cartilage, found in an unrelated study. Lung specimens from CD1 mice of 2, 6, 12, 18 or 24 months were fixed in 10% neutral-buffered formalin and paraffin-embedded. Apoptosis was analysed by in situ end-labelling of fragmented DNA. Proliferating cell nuclear antigen (PCNA) and nestin were examined by immunohistochemistry. Apoptosis and PCNA were detected in lung chondrocytes. Serial section analysis showed that cells in apoptosis were different from PCNA-positive cells, indicating that turnover was occurring. Chondrocytes were negative for nestin. Nestin-positive cells were present in connective tissue associated with cartilage, in some specimens in close proximity of it and in perivascular cells. Thus cell turnover in lung cartilage is possible, which may be mediated by nestin-positive cells.

Back to the Basics: Usefulness of Naturally Aged Mouse Models and Immunohistochemical and Quantitative Morphologic Methods in Studying Mechanisms of Lung Aging and Associated Diseases.

Aging-related molecular and cellular alterations in the lung contribute to an increased susceptibility of the elderly to devastating diseases. Although the study of the aging process in the lung may benefit from the use of genetically modified mouse models and omics techniques, these approaches are still not available to most researchers and produce complex results. In this article, we review works that used naturally aged mouse models, together with immunohistochemistry (IHC) and quantitative morphologic (QM) methods in the study of the mechanisms of the aging process in the lung and its most commonly associated disorders: cancer, chronic obstructive pulmonary disease (COPD), and infectious diseases. The advantage of using naturally aged mice is that they present characteristics similar to those observed in human aging. The advantage of using IHC and QM methods lies in their simplicity, economic accessibility, and easy interpretation, in addition to the fact that they provide extremely important information. The study of the aging process in the lung and its associated diseases could allow the design of appropriate therapeutic strategies, which is extremely important considering that life expectancy and the number of elderly people continue to increase considerably worldwide.

Nestin-Expressing Cells in the Lung: The Bad and the Good Parts.

Nestin is a member of the intermediate filament family, which is expressed in a variety of stem or progenitor cells as well as in several types of malignancies. Nestin might be involved in tissue homeostasis or repair, but its expression has also been associated with processes that lead to a poor prognosis in various types of cancer. In this article, we review the literature related to the effect of nestin expression in the lung. According to most of the reports in the literature, nestin expression in lung cancer leads to an aggressive phenotype and resistance to chemotherapy as well as radiation treatments due to the upregulation of phenomena such as cell proliferation, angiogenesis, and metastasis. Furthermore, nestin may be involved in the pathogenesis of some non-cancer-related lung diseases. On the other hand, evidence also indicates that nestin-positive cells may have a role in lung homeostasis and be capable of generating various types of lung tissues. More research is necessary to establish the true value of nestin expression as a prognostic factor and therapeutic target in lung cancer in addition to its usefulness in therapeutic approaches for pulmonary diseases.

Neurologically Asymptomatic Lumbar Traumatic Dislocation With Vascular Compression in a Patient With Ankylosing Spondylitis: Case Report.

BACKGROUND: Ankylosing spondylitis (AS) is associated with high rates of severe thoracolumbar fractures, in many cases with neurological deficits. It is currently a point of debate as to whether the optimal surgical treatment is posterior fixation and fusion or combined approaches. Vascular injuries in this kind of fracture are a challenging issue to solve in the management of these patients. METHODS: We are reporting the case of a 65-year-old man who presented an L4 traumatic fracture-dislocation. He had a long history of symptomatic AS. No neurological deficits were detected during the initial exploration. During the preoperative work-up, a lumbar spine computed tomography (CT) scan was taken with vascular reconstruction of the abdominal vessels. It confirmed the compression of the abdominal aorta, which had caused more than 90% stenosis. A posterior approach, an open reduction, and fixation with pedicle screws were performed, without hemodynamic or neurological changes. A postoperative angiography demonstrated a complete recovery of the vessel caliber, without contrast leaks. RESULTS: After a 2-year follow-up, the patient was pain free and the CT scan revealed bone fusion. CONCLUSIONS: The vascular structures involved in severe thoracolumbar fractures present a dangerous situation that should be considered in the choice of the surgical approach. The posterior approach alone may be a good option in the absence of vascular damage. However, due to risk of vessel rupture during the fracture reduction, vascular surgeons must take part in the surgery. LEVEL OF EVIDENCE: 5. CLINICAL RELEVANCE: The article provides help for surgeons who have to treat severe fractures in the context of ankylosing spondylitis.

Spontaneus involution of meningioma. Case report and literature review. / Involución espontánea de meningioma. Caso clínico y revisión de la literatura.

Meningiomas are tumors of the cerebral meninges, with slow growth and usually benign, whose treatment is essentially surgery. They have progesterone receptors, and to a lesser extent estrogen, which sometimes causes them to have growth or involution linked to hormonal treatment. Its spontaneous involution is extremely rare. We present the case of a male with a meningioma of the sphenoid planum. He had a history of diabetes mellitus, myasthenia gravis and prostate cancer. He was in treatment with analogs of GnRH (leuprorelin), antiandrogen (bicalutamide), ß3 agonists and α1 blockers. 15 months after the hormonal blockade, a reduction of the tumor of approximately 90% of its volume was detected. Previous reports show that treatment with gonadotropin analogues produces growth in some meningiomas. Other reports of spontaneous involution affect diabetic patients and patients in treatment with α1 blockers. Literature focus on meningiomas with spontaneous involution is reviewed.

Morphometric analysis of the non-epithelial areas of mouse bronchioles through the normal aging process.

Aging is associated with changes in the structure and function of the lung that may increase susceptibility to chronic lung diseases. The aim of this study was the morphometric assessment of the non-epithelial areas of the bronchioles of mouse through the normal aging process. Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Sections were cut, stained with Masson trichrome, and examined using a light microscope. High-resolution color images were captured using a camera linked to image analysis software to measure areas and lengths. We observed in the bronchioles through the aging process an increase of the total area, an increase of the lumen area, and a decrease of the wall area. In conclusion, our results revealed structural changes in the bronchioles of mouse through the normal aging process. These alterations are likely to contribute to development of chronic lung diseases.

C3435T polymorphism in the MDR1 gene and breast cancer risk in northeastern Mexico.

The multidrug resistance gene 1 (MDR1) encodes a membrane-bound phosphoglycoprotein (P-gp). It functions as a transmembrane efflux pump for various structurally unrelated carcinogens and toxins. Polymorphism C3435T of MDR1 has been investigated for its association with breast cancer in different populations. However, the results are inconsistent and inconclusive. The objective of this study was to determine whether an association exists between the MDR1 C3435T polymorphism and the risk of breast cancer in a population from northeastern Mexico, which displays ethnic characteristics that differentiate it from other populations of the country. Genotypes were determined for 243 women with histologically confirmed breast cancer and 118 control subjects. Polymorphism of MDR1 C3435T was analyzed by DNA microarray. We found an increased breast cancer risk associated with CT and CC genotypes (OR = 1.88, 95% CI: 1.04-3.39, P = 0.033 for CT vs. TT; OR = 2.91, 95% CI: 1.48-5.74, P = 0.001 for CC vs. TT). Furthermore, there was significantly increased risk of breast cancer associated with the C allele (OR = 1.59, 95% CI: 1.16-2.18, P = 0.003). In conclusion, we found an association between the MDR1 C3435T polymorphism and risk of breast cancer in subjects from northeastern Mexico. Identification of inter-individual variability in this polymorphism may be useful for individualizing breast cancer genetic screening and therapeutic intervention.

Current use of Social Media in Neurosurgery in Spain. / Situación actual del uso de redes sociales en Neurocirugía en España.

OBJECTIVE: To analyze the current situation in Spain of the use of Social Media in Neurosurgery. MATERIALS AND METHODS: We made an observational transversal study between February and March 2017, with a systematic search of the Facebook, Twitter and Youtube accounts from public and private neurosurgical units, scientific societies, peer-reviewed publications and patients groups in relation with Neurosurgical pathologies. We rank them according their popularity. RESULTS: According of our search only 5 public neurosurgical services have social media accounts, being their popularity inferior to the private units accounts. In relation with the scientific societies and neurosurgical publications their presence in social media is marginal, even more in comparison to the accounts of other medical specialities. The popularity of associations of patients and supporting groups is high, especially among patients, finding there more information about their disease. CONCLUSIONS: The use in Spain of Social Media about Neurosurgery is low in comparison to other medical specialities. There is a huge field to improve the popularity of the accounts, making in them promotion of health and extend the diffusion of the scientific society and the peer-reviewed publication Neurocirugía.

Multiple filum terminale hemangioblastomas symptomatic during pregnancy. Case report.

Hemangioblastomas are low-grade, highly vascular tumors commonly associated with von Hippel-Lindau (VHL) syndrome and most often appearing in the cerebellum. They very rarely occur in the spinal nerve roots, and an origin in the filum terminale is exceptional with no instances of multiple hemangioblastomas of the filum terminale reported in the literature. Because of their vascular nature, these lesions can enlarge and become symptomatic in the context of the changes that take place during pregnancy, as has been noted with cerebellar hemangioblastomas. In any case, the evolution of spinal hemangioblastomas during pregnancy is not well known given its rarity. The conjunction of both processes--that is, multiple hemangioblastomas arising in the filum terminale and pregnancy--is unique. The authors describe the case of a 41-year-old woman with multiple hemangioblastomas of the filum terminale and no other evidence of VHL syndrome, in whom pregnancy precipitated symptoms. The interruption of gestation led to a remission of the symptoms. The literature concerning filum terminale hemangioblastomas and pregnancy is also reviewed.