Atlantoaxial instability secondary to Bartonella henselae osteomyelitis managed surgically by atlantoaxial instrumentation: A case report and systematic review.

Cat scratch disease (CSD), caused by Bartonella henselae, may atypically present with vertebral osteomyelitis. Antibiotic regimens are tailored to presentation, which is markedly variable and not well defined for any atypical disease. In cases of spinal instability, the use of antibiotics alone may not be sufficient. Atlantoaxial instability caused by osteomyelitis is a rare complication of CSD. In this report, we describe the rare case of vertebral osteomyelitis complicated by atlantoaxial instability, requiring both antibiotics and atlantoaxial fusion. We discuss our case, surgical technique, rationale, and outcome. In addition, we conducted a systematic review of the literature of vertebral osteomyelitis in pediatric secondary to B. henselae. A 2-year-old child presented with a 2-month history of irritability, fever, and rigid neck pain along with a recent history of feline exposure. Physical examination revealed cervical tenderness and decreased range of motion. Computed tomography (CT) showed osteolysis of the right C1 lateral mass and pars articularis; T1-weighted magnetic resonance imaging with contrast showed enhancement around the right C1 lateral mass. The titer for B. henselae was high. A diagnosis of cat scratch osteomyelitis with cervical instability was made, for which the patient underwent surgery with atlantoaxial fusion. Postoperative imaging demonstrated resolution of the contrast-enhanced lesion. At 6-year follow-up, the patient showed no signs of residual complications from surgical intervention with a solid fusion. Our review revealed 44 cases of pediatric CSD vertebral osteomyelitis. Conservative management with antibiotic employed in 86% while antibiotics with surgical intervention in 14% of the cases. Surgical intervention was most often in the form of incision for drainage and decompression without fusion. Average follow-up 10 months with 86% achieved complete resolution. Cervical instability caused by osteolysis is a rare complication of CSD. This can subsequently lead to vertebral instability, requiring definitive surgical intervention.

Patient-reported outcome measures in spine surgery: A systematic review.

Background: Steadily increasing expenditure in the United States health-care system has led to a shift toward a value-based model that focuses on quality of care and cost-effectiveness. Operations involving the spine rank among some of the most common and expensive procedures performed in operating rooms nationwide. Patient-reported outcomes measures (PROMs) are a useful tool for reporting levels of outcome and analyzing patient recovery but are both under-utilized and nonstandardized in spine surgery. Methods: We conducted a systematic review of the literature using the PubMed database, focusing on the most commonly utilized PROMs for spine disease as well as spinal deformity. The benefits and drawbacks of these PROMs were then summarized and compared. Results: Spine-specific PROMs were based on the class of disease. The most frequently utilized PROMs were the Neck Disability Index and the modified Japanese Orthopaedic Association scale; the Oswestry Disability Index and the Roland-Morris Disability Questionnaire; and the Scoliosis Research Society 22-item questionnaire (SRS-22) for cervicothoracic spine disease, lumbar spine disease, and spinal deformity, respectively. Conclusion: We found limited, though effective, use of PROMs targeting specific classes of disease within spine surgery. Therefore, we advocate for increased use of PROMs in spine surgery, in both the research and clinical settings. PROM usage can help physicians assess subjective outcomes in standard ways that can be compared across patients and institutions, more uniquely tailor treatment to individual patients, and engage patients in their own medical care.

Competition between bridged dinucleotides and activated mononucleotides determines the error frequency of nonenzymatic RNA primer extension.

Nonenzymatic copying of RNA templates with activated nucleotides is a useful model for studying the emergence of heredity at the origin of life. Previous experiments with defined-sequence templates have pointed to the poor fidelity of primer extension as a major problem. Here we examine the origin of mismatches during primer extension on random templates in the simultaneous presence of all four 2-aminoimidazole-activated nucleotides. Using a deep sequencing approach that reports on millions of individual template-product pairs, we are able to examine correct and incorrect polymerization as a function of sequence context. We have previously shown that the predominant pathway for primer extension involves reaction with imidazolium-bridged dinucleotides, which form spontaneously by the reaction of two mononucleotides with each other. We now show that the sequences of correctly paired products reveal patterns that are expected from the bridged dinucleotide mechanism, whereas those associated with mismatches are consistent with direct reaction of the primer with activated mononucleotides. Increasing the ratio of bridged dinucleotides to activated mononucleotides, either by using purified components or by using isocyanide-based activation chemistry, reduces the error frequency. Our results point to testable strategies for the accurate nonenzymatic copying of arbitrary RNA sequences.

Spinal pigmented villonodular synovitis and tenosynovial giant cell tumor: A report of two cases and a comprehensive systematic review.

BACKGROUND AND OBJECTIVE: Pigmented villonodular synovitis (PVNS) is a lesion of uncertain etiology that involves the synovial membranes of joints or tendon sheaths, representing a diffuse and non-encapsulated form of the more common giant cell tumors of the synovium (GCTTS). PVNS was reclassified to denote a diffuse form of synovial giant cell tumor (TSGCT), while 'giant cell tumor of the tendon sheath (GCTTS)' was used for localized lesions. These pathologies rarely affect the axial skeleton. We provide an unprecedented and extensive systematic review of both lesions highlighting presentation, diagnostic considerations, treatment, prognosis, and outcomes, and we report a short case-series. METHOD: We describe two-cases and conduct a systematic review in accordance with PRISMA guidelines. RESULT: PVNS was identified in most of the cases reviewed (91.6 %), manifesting predominantly in the cervical spine (40 %). Patients commonly presented with neck pain (59 %), back pain (53 %), and lower back pain (81.2 %) for cervical, thoracic, and lumbar lesions, respectively. GTR occurred at rates of 94 %, 80 %, and 87.5 %. Recurrence was most common in the lumbar region (30.7 %). GCTTS cases (8%) manifested in the cervical and thoracic spine at the same frequency. We reported first case of GCTTS in the lumbosacral region. Both poses high rate of facet and epidural involvements. CONCLUSION: Spinal PVNS and GCTTS are rare. These lesions manifest most commonly as PVNS within the cervical spine. Both types have a high rate of facet and epidural involvement, while PVNS has the highest rate of recurrence within the lumbar spine. The clinical and radiological features of these lesions make them difficult to differentiate from others with similar histogenesis, necessitating tissue diagnosis. Proper management via GTR resolves the lesion, with low rates of recurrence.

The Global Burden of Neural Tube Defects and Disparities in Neurosurgical Care.

BACKGROUND: Despite the success of folic acid fortification programs, neural tube defects (NTDs) such as spina bifida, encephalocele, and anencephaly remain among the most substantial causes of childhood morbidity and mortality worldwide. Although these are complicated conditions that require an interdisciplinary approach to care, definitive treatment of survivable NTDs is often neurosurgical. METHODS: Using Global Burden of Disease data, we examined the global burden of NTDs as related to a nation's wealth, health care quality, and access to neurosurgical care. We abstracted data for death by cause, years lived with disability (YLD), gross domestic product (GDP), United Nations geoscheme, Food Fortification Initiative participation, and Healthcare Access and Quality Index. We compared means using 1-way analysis of variance and proportions using Fisher exact tests, with statistical significance as α = 0.05. RESULTS: Seventeen of 20 (85%) nations with the most deaths caused by NTDs (P < 0.0001) and 15/20 (75%) nations with the highest YLD (P < 0.0001) were in the lowest GDP quartile. Deaths and YLD were negatively correlated with increasing GDP and Healthcare Access and Quality Index (P < 0.0001). The nations with the highest disease burdens also had the fewest neurosurgeons per capita. CONCLUSIONS: Despite the success of folic acid fortification programs, greater global public health efforts should be placed on improving access to neurosurgical care in low and middle-income nations through sustainable initiatives such as surgeon exchange programs and the establishment of neurosurgery residency training programs.

Biomass-derived porous carbonaceous materials and their composites as adsorbents for cationic and anionic dyes: A review.

Currently used textile dyes are not highly toxic or carcinogenic, but the intense and persistent color of the effluent is problematic. Of the remediation processes investigated, the adsorption process is attractive, and carbonaceous adsorbents (CAs) are ideal for that purpose because of their very high dye-binding capacity (DBC). In this review, the potential of biomass-based feedstocks to produce CAs and the application of the produced adsorbents for the removal of various types of dyes from effluent have been compiled and critically reviewed. The effect of preparation conditions on the surface area, porosity, pore volume, and chemical characteristics of the produced CAs has been outlined and discussed. The DBC of various CAs at the optimum conditions has been compiled, and dye-binding mechanisms, dye sorption isotherm models, the stability of adsorbents, and regeneration methods of CAs are discussed. The analysis of the compiled dye-adsorption data shows that the dye-adsorption capacity of some CAs derived from biomasses and their composites is considerably higher than the commercially available activated carbon (AC) adsorbents. For example, a commercial AC (Filtrasorb-400) showed 400 mg/g DBC for the C.I. Reactive Red 120 dye. Conversely, the CS-DB adsorbent showed excellent anionic and cationic DBC for C.I. Direct Red 28 and C.I. Basic Green 4 dyes, 20317 and 12502 mg/g respectively. The porous carbon/polyvinyl alcohol hydrogel and GO/zeolitic imidazolate framework composite adsorbents exhibited dye-adsorption capacity as high as 13381.6 and 3300 mg/g respectively. The pore volume and functional groups of dyes are the deciding factors in achieving high dye adsorption.

Symptomatic xanthogranuloma of the lateral ventricle in a pregnant patient treated with delayed resection: A case report and systematic review.

Intracranial xanthogranulomas (XG) are a rare benign histiocytic neoplasm and most often within the choroid. The majority are asymptomatic and are found incidentally on imaging or post-mortem examination or autopsy. We present a case of symptomatic XG in a pregnant patient who underwent a delayed transcortical, transventricular approach for lateral ventricle XG resection following the completion of her pregnancy. Four years post-operatively, the patient is neurologically intact and without recurrence. Our review of the literature showed differences among XG depending on location. The clinical and radiological features of XG are often indistinguishable from tumors arising from the choroid plexus and should be considered as a rare etiology in the differential of newly diagnosed intraventricular lesions.

Adult Pineal Region Atypical Teratoid Rhabdoid Tumor: A Case for Aggressive Surgical and Chemoradiation Management with Comprehensive Literature Review.

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant central nervous system neoplasm classified as an embryonal grade IV neoplasm by the World Health Organization. ATRT generally occurs in children younger than 3 years, with 85 pathologically confirmed cases reported in adults. It is most commonly supratentorial, with only 9 confirmed adult cases localized to the pineal region. CASE DESCRIPTION: The case is described of a 29-year-old man with a history of chronic migraines and a previously negative computed tomography scan of the head presenting with worsening headaches and new-onset diplopia with upward gaze palsy. Computed tomography and magnetic resonance imaging showed a hemorrhagic pineal mass with extension into the right thalamus. After resection, the immunohistochemical staining and cytogenetic profile proved consistent with ATRT, making it the ninth reported case of pineal ATRT in an adult, which was treated aggressively with good outcome. CONCLUSIONS: Adult ATRT is rare, especially in the pineal region, with only 9 cases reported. Because of the aggressiveness, ATRT must be considered in the differential diagnosis of pineal region lesions because early diagnosis and aggressive treatment are key to prolonged survival.

Treatment with dimethyl fumarate reduces the formation and rupture of intracranial aneurysms: Role of Nrf2 activation.

Oxidative stress and chronic inflammation in arterial walls have been implicated in intracranial aneurysm (IA) formation and rupture. Dimethyl fumarate (DMF) exhibits immunomodulatory properties, partly via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which reduces oxidative stress by inducing the antioxidant response element (ARE). This study evaluated the effects of DMF both in vitro, using tumor necrosis factor (TNF)-α-treated vascular smooth muscle cells (VSMC), and in vivo, using a murine elastase model to induce aneurysm formation. The mice were treated with either DMF at 100 mg/kg/day P.O. or vehicle for two weeks. DMF treatment protected VSMCs from TNF-α-induced inflammation as demonstrated by its downregulation of cytokines and upregulation of Nrf2 and smooth muscle cell markers. At higher doses, DMF also inhibited the pro-proliferative action of TNF-α by increasing apoptosis which protected the cells from aponecrosis. In mice, DMF treatment significantly decreased the incidence of aneurysm formation and rupture, at the same time increasing Nrf2 levels. DMF demonstrated a neuroprotective effect in mice with a resultant inhibition of oxidative stress, inflammation, and fibrosis in the cerebrovasculature. This suggests a potential role for DMF as a rescue therapy for patients at risk for formation and rupture of IAs.

Cauda Equina Syndrome Secondary to Diffuse Infiltration of the Cauda Equina by Acute Myeloid Leukemia: Case Report and Literature Review.

BACKGROUND: Cauda equina syndrome (CES) results from the dysfunction of the lumbar, sacral, and coccygeal rootlets composing the cauda equina. The underlying etiology is most commonly compression secondary to a large herniated lumbosacral disk; however, any pathology affecting the rootlets can result in the syndrome. METHODS: We present a rare case of CES secondary to neoplastic polyradiculitis in a patient with acute myelogenous leukemia (AML) and review the pertinent literature. A 72-year-old male with a medical history of AML presented with 2 weeks of difficulty ambulating, followed by acute-onset low back pain radiating to the buttocks bilaterally. RESULTS: Imaging of the lumbar spine demonstrated diffuse enhancement and thickening of the cauda equina rootlets. Lumbar puncture showed numerous blasts with monocytoid features consistent with AML, and the patient was diagnosed with polyradiculopathy of the cauda equina secondary to diffuse metastatic infiltration. CONCLUSIONS: Central nervous system involvement of leukemia is poorly understood, even though such lesions are not uncommon in advanced disease. As treatment has improved, many types of leukemia, such as AML, are believed to be curable, and patients with the disease are living longer. With improved survival, it is reasonable to suspect that such involvement by AML may become more common. Our patient is a classic presentation of CES secondary to diffuse infiltration by AML and serves as an example of this rare manifestation of hematologic malignancy.

Surgical Approaches in the Treatment of Intracranial Complications of Paranasal Sinus Disease: A Review of the Literature.

BACKGROUND: Intracranial extension of frontal or ethmoid sinusitis carries a high morbidity and mortality if not treated aggressively. With the emergence of endoscopic sinus surgery (ESS), we questioned whether these approaches have supplanted traditional transcranial procedures for intracranial extension of sinus disease, and whether ESS approaches had a difference in patient outcomes. METHODS: Studies reporting surgical management and outcomes of frontal sinus disease with intracranial extension were queried using the United States National Library of Medicine at the National Institutes of Health PubMed database. We also queried common internet search engines. We included studies regarding sinogenic intracranial suppurative infections treated surgically with ESS and neurosurgical approaches. Studies with insufficient data regarding specific treatment methods and studies that included populations of medically treated infections were excluded. RESULTS: A total of 108 cases were identified in which patients with intracranial sinogenic disease were treated via ESS alone (morbidity: 43.5%, mortality: 0.9%), 47 cases via transcranial intervention alone (morbidity: 33.2%, mortality: 7.8%), and 43 cases via simultaneous neurosurgical and ESS approaches (morbidity: 16.3%, mortality: 6.4%). Complex sinus disease with posterior table compromise in the absence of intracranial extension treated via ESS alone was reported in 164 cases with a morbidity and mortality of 3.8% and 0%, respectively. CONCLUSIONS: Combined ESS and transcranial approaches achieve definitive control of sinogenic and intracranial disease, whereas either modality alone carries a potential risk for higher morbidity and mortality. The use of ESS alone may have use in the treatment of sinusitis with posterior table erosion prior to intracranial extension.

Biomarkers of Pineal Region Tumors: A Review.

Background: The pineal gland, a small, pinecone-shaped organ deep within the brain, is responsible for producing melatonin. The gland consists of pineal parenchymal cells and glial cells that can form neoplasms. Pineal region neoplasms can also arise from germ cells and adjacent structures. This review focuses on detection of serum and cerebrospinal fluid (CSF) biomarkers of germ cell tumors and pineal parenchymal cell tumors, as these types comprise most neoplasms specific to the pineal region. Methods: For this review, we searched PubMed using the following keywords: biomarkers, germ cell tumor, germinoma, melatonin, pineal, pineal gland, pineal neoplasm, pinealoma, pineal parenchymal cell tumor, pineal region, and pineal tumor. We limited our search to full-text English articles and identified other relevant sources from the reference lists of identified articles. Results: Serum and CSF biomarker assays have a role in cases of suspected pineal germ cell or parenchymal neoplasms. Biomarkers including alpha-fetoprotein, beta-human chorionic gonadotropin, and placental alkaline phosphatase inform diagnosis and treatment and are important for monitoring germ cell tumor response to treatment. No biomarkers are currently available that inform diagnosis or treatment of pineal parenchymal tumors, although melatonin assays may have a role in monitoring response to treatment. Conclusion: Serum and CSF biomarkers in conjunction with clinical and radiographic evidence of a pineal region mass can inform the decision whether to undertake stereotactic biopsy or surgical excision or whether to proceed straight to medical treatment.

Advances in Neuro-Oncology Imaging Techniques.

BACKGROUND: Central nervous system (CNS) tumors are a rare but devastating malignancy, often robbing patients of the basic quality of life. Despite advances in our understanding of the CNS tumor disease processes, the prognosis for patients with CNS tumors remains poor. Better characterization and diagnostic and monitoring approaches are necessary to assist in diagnosis and treatment of CNS tumors. One important tool in the neuro-oncology armamentarium is the use of advanced imaging techniques. METHODS: We searched PubMed using the keywords neuro-oncology imaging, pseudoprogression, molecular imaging, and biomarkers. We limited our search to full-text English articles and identified other relevant articles from the reference lists of previously identified articles. RESULTS: Advances in imaging techniques have allowed investigators to explore various imaging modalities, from tumor characterization to differentiating pseudoprogression from tumor progression. Better imaging can result in better diagnostic approaches, greater and safer resection techniques, and improved monitoring of tumor progression. CONCLUSION: This review highlights advances in neuro-oncology imaging techniques and their clinical utility in the treatment and management of primary brain tumors.

Decompressive Medial Cuneiform Exostectomy for Resistant Tibialis Anterior Insertional Tendinopathy.

Distal tibialis anterior tendinopathy, as a clinical entity, has only recently been documented in foot and ankle studies. We report our experience with medial cuneiform decompressive exostectomy and superficial tendon debridement in 14 cases of recalcitrant tibilalis anterior insertional pain. We reviewed 13 patients (14 feet; 12 females, 1 male; mean age 67.9 ± 7.5; range 55 to 80 years) in whom conservative treatment had failed who had undergone debridement of the insertional tibialis anterior tendon and decompressive exostectomy of the medial cuneiform. Pre- and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scale and visual analog scale (VAS) pain scores, local clinical findings, and dorsiflexion power at an average follow-up period of 28 ± 17.9 (range 6 to 55) months were assessed. All patients had experienced burning, nocturnal, medial midfoot pain and disability. The symptom longevity preoperatively was 8.5 ± 3.1 (range 6 to 17) months. Peritendinous or intrasubstance signal changes were noted on magnetic resonance imaging in 10 feet (71%). The mean preoperative VAS pain score was 8.7 ± 1.3 (range 5 to10), whereas postoperative it was 0.4 ± 0.5 (range 0 to1) (p = .001). The mean preoperative and postoperative AOFAS midfoot scale score was 54 ± 14.5 (range 20 to 70) and 91 ± 6.8 (range 79 to 100), respectively (p = .001). Postoperative ankle dorsiflexion power was normal and local tenderness had resolved in all patients. One patient (7.1%) stumbled at 2 weeks, resulting in avulsion of the tibialis anterior tendon, requiring transosseous fixation and gastrocnemius recession. All patients reported satisfaction with the surgical outcome and willingness to undergo the surgery again if necessary. A combination of medial cuneiform mechanical decompression and insertional tendon debridement can offer successful outcomes in resistant insertional tibialis anterior tendinopathy.

Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys.

Background: Renal anastomosing hemangioma (RAH) is an extremely rare benign vascular tumor first described in 2009. Making this diagnosis is fraught with challenges. Radiologically they share features consistent with renal cell carcinomas (RCCs). Their vascular nature poses risks if considering preoperative biopsy and histologically they share characteristics akin to angiosarcomas. The few reports published in the literature suggest presentation with hematuria, flank pain, and polycythemia although the majority are diagnosed at postnephrectomy histologic examination. This case represents the first metachronous RAH in the literature, and is the first RAH presenting with severe hemorrhage. Case Presentation: A 62-year-old woman of Albanian heritage presented to urology with visible hematuria and positive urine cytology. Three years before this presentation, she had undergone an elective radical right-sided nephrectomy for a suspected RCC detected on magnetic resonance imaging, which proved to be an RAH after postoperative histologic examination of the specimen. The patient was investigated with cystoscopy and ureteroscopy for this new hematuria presentation, both of which were unremarkable. Fourteen hours post ureteroscopy, the patient became severely hypotensive and developed acute kidney injury. A CT scan indicated a large left-sided renal subcapsular and retroperitoneal hematoma that was actively bleeding. The patient was hemodynamically unstable and, therefore, required an emergency open left-sided nephrectomy, rendering her anephric and dialysis dependent. Postoperative histologic examination proved that the left kidney also contained an RAH. Conclusion: The anastomosing hemangioma is an important subtype to differentiate from angiosarcoma before and after a nephrectomy. Urologists should carefully consider invasive tests in patients with previously diagnosed vascular lesions as there may be an increased risk of bleeding. Patients with a previously diagnosed anastomosing hemangioma may require surveillance of the contralateral kidney.

An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.

Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.

Aberrant autolysosomal regulation is linked to the induction of embryonic senescence: differential roles of Beclin 1 and p53 in vertebrate Spns1 deficiency.

Spinster (Spin) in Drosophila or Spinster homolog 1 (Spns1) in vertebrates is a putative lysosomal H+-carbohydrate transporter, which functions at a late stage of autophagy. The Spin/Spns1 defect induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms, but little is known about the mechanisms leading to the pathogenesis in vivo. Beclin 1 and p53 are two pivotal tumor suppressors that are critically involved in the autophagic process and its regulation. Using zebrafish as a genetic model, we show that Beclin 1 suppression ameliorates Spns1 loss-mediated senescence as well as autophagic impairment, whereas unexpectedly p53 deficit exacerbates both of these characteristics. We demonstrate that 'basal p53' activity plays a certain protective role(s) against the Spns1 defect-induced senescence via suppressing autophagy, lysosomal biogenesis, and subsequent autolysosomal formation and maturation, and that p53 loss can counteract the effect of Beclin 1 suppression to rescue the Spns1 defect. By contrast, in response to DNA damage, 'activated p53' showed an apparent enhancement of the Spns1-deficient phenotype, by inducing both autophagy and apoptosis. Moreover, we found that a chemical and genetic blockage of lysosomal acidification and biogenesis mediated by the vacuolar-type H+-ATPase, as well as of subsequent autophagosome-lysosome fusion, prevents the appearance of the hallmarks caused by the Spns1 deficiency, irrespective of the basal p53 state. Thus, these results provide evidence that Spns1 operates during autophagy and senescence differentially with Beclin 1 and p53.

Radiation resistance of sequencing chips for in situ life detection.

Life beyond Earth may be based on RNA or DNA if such life is related to life on Earth through shared ancestry due to meteoritic exchange, such as may be the case for Mars, or if delivery of similar building blocks to habitable environments has biased the evolution of life toward utilizing nucleic acids. In this case, in situ sequencing is a powerful approach to identify and characterize such life without the limitations or expense of returning samples to Earth, and can monitor forward contamination. A new semiconductor sequencing technology based on sensing hydrogen ions released during nucleotide incorporation can enable massively parallel sequencing in a small, robust, optics-free CMOS chip format. We demonstrate that these sequencing chips survive several analogues of space radiation at doses consistent with a 2-year Mars mission, including protons with solar particle event-distributed energy levels and 1 GeV oxygen and iron ions. We find no measurable impact of irradiation at 1 and 5 Gy doses on sequencing quality nor on low-level hardware characteristics. Further testing is required to study the impacts of soft errors as well as to characterize performance under neutron and gamma irradiation and at higher doses, which would be expected during operation in environments with significant trapped energetic particles such as during a mission to Europa. Our results support future efforts to use in situ sequencing to test theories of panspermia and/or whether life has a common chemical basis.

Radiation resistance of biological reagents for in situ life detection.

Life on Mars, if it exists, may share a common ancestry with life on Earth derived from meteoritic transfer of microbes between the planets. One means to test this hypothesis is to isolate, detect, and sequence nucleic acids in situ on Mars, then search for similarities to known common features of life on Earth. Such an instrument would require biological and chemical components, such as polymerase and fluorescent dye molecules. We show that reagents necessary for detection and sequencing of DNA survive several analogues of the radiation expected during a 2-year mission to Mars, including proton (H-1), heavy ion (Fe-56, O-18), and neutron bombardment. Some reagents have reduced performance or fail at higher doses. Overall, our findings suggest it is feasible to utilize space instruments with biological components, particularly for mission durations of up to several years in environments without large accumulations of charged particles, such as the surface of Mars, and have implications for the meteoritic transfer of microbes between planets.

5q14.3 neurocutaneous syndrome: a novel continguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C.

Haploinsufficiency of RASA1, located on chromosome 5q14.3, has been identified as the etiology underlying the disorder capillary malformation-arteriovenous malformation (CM-AVM). Recently, haploinsufficiency of MEF2C, located 1.33 Mb distal to RASA1 on chromosome 5q14.3, has been implicated as the genetic etiology underlying a complex array of deficits including mental retardation, hypotonia, absent speech, seizures, and brain anomalies. Here we report a patient who is haploinsufficient in both RASA1 and MEF2C who presents with dermatologic and neurologic abnormalities that constitute a 5q14.3 neurocutaneous syndrome. This finding highlights the need to assess for CM-AVM in patients with neurologic features consistent with MEF2C haploinsufficiency, and vice versa.