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OBJECTIVE This study evaluated urinary angiotensinogen in preeclampsia. METHODS Normal pregnant (n = 57) and preeclamptic patients (n = 31); Normal pregnant (n = 10) and preeclamptic rats (n = 10) were studied. Urinary angiotensinogen and plasma angiotensin II were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS Urinary angiotensinogen in preeclampsia patients (2.0 ± 1.1 ng/mg creatinine) was suppressed (*p

ObjectiveThe Buffalo Concussion Physical Examination (BCPE) is a brief, but pertinent physical examination designed for the subacute, outpatient assessment of concussion. The purpose of this study was to perform the BCPE on a larger sample and derive a scoring system to identify children at risk for Persistent Post-Concussive Symptoms (PPCS, recovery ≥30 days).MethodsThis prospective, observational cohort study from September 2016 to March 2019 was performed at three university-affiliated concussion clinics. Male and female children (n=270, 14.92±1.86 years, range 8–18, 38% female) were diagnosed with a concussion within 14 days of injury and followed-up until recovery. Logistic regression was used with history and physical examination variables to predict PPCS and a weighted scoring metric was derived.ResultsOut of 15 predictor variables, the main effects of 1 preinjury variable (≥3 previous concussions), 2 injury characteristic variables (days-since-injury and type-of-injury), 3 physical examination variables (orthostatic intolerance (OI), vestibulo-ocular reflex (VOR) and tandem gait) and 2 interaction terms (OI/VOR and tandem gait/type-of-injury) produced a score that was 85% accurate for identifying children with low-risk, medium-risk and high-risk for PPCS on cross-validation.ConclusionThe Risk for Delayed Recovery (RDR)-Score allows physicians in an outpatient setting to more accurately predict which children are at greater risk for PPCS early after their injury, and who would benefit most from targeted therapies. The RDR-Score is intended to be used as part of a comprehensive assessment that should include validated symptom checklists, mental health history and adjunct testing (eg, cognitive or physical exertion) where clinically indicated.

The Buffalo Concussion Treadmill Test (BCTT) is a safe and validated tool to assess exercise tolerance after sport-related concussion (SRC). Sex differences may affect the interpretation of this systematic exertion test in the concussed population, which is important for clinicians. The purpose of this study was to examine sex differences in BCTT performance in adolescents with acute SRC.Prospective cohort.Male (n = 103, 15.3 ± 2 years) and female (n = 87, 15.1 ± 2 years) adolescents with SRC performed the BCTT within 10 days of injury. Heart rate (HR), HR threshold (HRt), Delta HR (difference between resting HR and HRt), symptom severity on Visual Analog Scale (VAS) and symptoms exacerbated on the BCTT were collected and compared.Males had lower resting HR (M: 70.9 ± 12 vs F: 75.7 ± 13 bpm, p 0.01) and reached a lower HRt than females (M: 134.7 ± 23 vs F: 141.5 ± 25 bpm, p = 0.05). Sexes did not differ on Delta HR (M: 63.8 ± 26 vs F: 65.9 ± 24 bpm, p = 0.57), total treadmill time (M: 9.3 ± 5 vs F: 8.4 ± 4 min, p = 0.20), maximum VAS (M: 5.0 ± 2 vs F: 5.4 ± 2, p = 0.18) or incidence of a change in VAS (M: 91% vs F: 94%, p = 0.43) on the BCTT.Although males may reach symptom exacerbation at a slightly lower mean HRt than females on the BCTT within 10 days of SRC, the BCTT provides comparable information and both sexes reach symptom exacerbation at similar Delta HR.

الملخص: سرطان الغدد الليمفاوية بيركيت، هو سرطان يصيب الغدد الليمفاوية اللاهودجكينية من النوع ب (الخلايا اللِّمفاوية أو اللِّمفاويَّات البائيَّة). انسداد الوريد الأجوف العلوي يُعتبر من النادر حدوثه مع سرطان الغدد الليمفاوية بيركيت، وهو غالبا يحدث مع الأنواع الأخرى من سرطان الغدد الليمفاوية اللاهودجكيِنية مثل سرطان الخلايا الكبيرة. نبلغ في هذا التقرير عن حالة نادرة لسرطان الغدد الليمفاوية بيركيت من النوع المتفرق مع انسداد الوريد الأجوف العلوي لدى صبي يبلغ من العمر ١٦ عاما مصابا بكتل سرطانية في البلعوم، المنصف الصدري والغدة الكظرية. المريض أتى بانتفاخ في الجزء الأيسر العلوي من الرقبة لمدة شهرين، مع ازدياد الحجم مع مرور الوقت بدون أيَة أعراض أخرى، وفي اليوم الثاني من التنويم تم اختبار المريض لفايروس كورونا (كوفيد-١٩) وكانت النتيجة إيجابية. في الفحص السريري كان لديه انتفاخ في الغدة اللمفاوية الرقبية وانتفاخان في الجهتين من الغدد اللمفاوية الأذنية الخلفية. لم يكن هناك شيئا ملحوظا في الاختبار الصدري باستثناء بعض الدوالي الوريدية على صدر المريض. لم يكن هناك أية أعراض أو علامات لانسداد الوريد الأجوف العلوي بغض النظر عن نتائج الأشعة المقطعية. بدأ المريض على العلاج الكيميائي المكثف، وكانت لديه استجابة ملحوظة للعلاج في الكتل السرطانية في البلعوم والمنصف الصدري، مع استجابة طفيفة للكتلة السرطانية في الغدة الكظرية. لم يكن هناك أيَة مضاعفات ملحوظة. Abstract: Burkitt's lymphoma (BL) is an aggressive non-Hodgkin B-cell lymphoma. Superior vena cava obstruction (SVCO) is considered a rare presentation of BL and it is usually associated with other types of non-Hodgkin lymphoma such as diffuse large-cell. We report a rare case of sporadic BL with SVCO in a 16-year-old boy with nasopharyngeal, mediastinal, and adrenal masses. The patient presented with a two-month history of left upper neck swelling that increased with time and was not associated with other symptoms. The patient tested positive for COVID-19 on the second day after admission. On examination, he had enlarged solitary lateral cervical and bilateral posterior auricular lymph nodes. There were no signs or symptoms of SVCO regardless of the findings suggested by the computed tomography of the chest. The patient was treated with hyper-CVAD chemotherapy and showed a remarkable resolution of the nasopharyngeal and mediastinal masses with a mild response of his adrenal mass. There were no complications detected during this patient's management.

Objective The goals of this study were to assess the ability of salivary non-coding RNA (ncRNA) levels to predict post-concussion symptoms lasting ≥ 21 days, and to examine the ability of ncRNAs to identify recovery compared to cognition and balance. Methods RNA sequencing was performed on 505 saliva samples obtained longitudinally from 112 individuals (8–24-years-old) with mild traumatic brain injury (mTBI). Initial samples were obtained ≤ 14 days post-injury, and follow-up samples were obtained ≥ 21 days post-injury. Computerized balance and cognitive test performance were assessed at initial and follow-up time-points. Machine learning was used to define: (1) a model employing initial ncRNA levels to predict persistent post-concussion symptoms (PPCS) ≥ 21 days post-injury; and (2) a model employing follow-up ncRNA levels to identify symptom recovery. Performance of the models was compared against a validated clinical prediction rule, and balance/cognitive test performance, respectively. Results An algorithm using age and 16 ncRNAs predicted PPCS with greater accuracy than the validated clinical tool and demonstrated additive combined utility (area under the curve (AUC) 0.86; 95% CI 0.84–0.88). Initial balance and cognitive test performance did not differ between PPCS and non-PPCS groups (p > 0.05). Follow-up balance and cognitive test performance identified symptom recovery with similar accuracy to a model using 11 ncRNAs and age. A combined model (ncRNAs, balance, cognition) most accurately identified recovery (AUC 0.86; 95% CI 0.83–0.89). Conclusions ncRNA biomarkers show promise for tracking recovery from mTBI, and for predicting who will have prolonged symptoms. They could provide accurate expectations for recovery, stratify need for intervention, and guide safe return-to-activities.

Purpose Different approaches have been proposed to treat malocclusion secondary to the treatment of maxillofacial trauma. This study aimed to investigate the efficacy of prosthodontic treatment, orthodontic treatment, and implant-supported rehabilitation for the management of secondary malocclusion after maxillofacial trauma. Study selection: We searched five electronic databases and hand searched eight journals. The types of studies included were randomized controlled trials, cohorts, case–controls, and case series with at least eight patients with maxillofacial trauma and postoperative malocclusion. These studies used prosthetic treatment and implant-supported rehabilitation for secondary malocclusion after maxillofacial trauma. Risk of bias of eligible studies to be included in the final analysis was assessed independently by two authors using a tool for methodological quality assessment and synthesis of case series and case reports. Results After initial screening and identification of titles and abstracts, full text of 44 articles were found and evaluated against inclusion criteria. Of these 42 articles were excluded and remaining two were included in the review. Both the studies were case series with moderate to high risk of bias. Conclusions Both prosthetic treatment and implant-supported rehabilitation have the potential to restore secondary malocclusion after maxillofacial trauma. However, because less number of well-designed studies with high risk of bias were included in this systematic review, the findings should be interpreted with caution. Well-designed high-quality studies are required to draw definitive conclusions.

Introduction. A pancreatic pseudocyst (PP) with major diameter equal to 10 cm or more is called a giant pseudocyst. The ideal management for giant PPs is controversial. Endoscopic drainage is an alternative nonsurgical approach for PP management. Only a few cases of giant PPs were reported to be managed by endoscopic drainage. Case Presentation. We reported two cases of giant PPs following an episode of acute pancreatitis. Both were resolved following endoscopic cystogastrostomy using metallic and double-pigtail stents with excellent outcomes. There was no history of recurrence or complications on follow-up. In addition, we extensively reviewed all available literature studies of giant pancreatic pseudocyst presentation, management, and complications. We summarized all reported cases and presented them in a comprehensive table. Conclusion. The endoscopic cystogastrostomy approach is cost saving, can avoid surgical complications, and offers an early hospital discharge.

Meningovascular neurosyphilis is a common cause of stroke in young adults, particularly when HIV co-infection is present. Contemporary screening for neurosyphilis relies on invasive testing. High resolution vessel wall imaging (HR-VW) is an emerging non-invasive tool to detect intracranial vessel wall inflammation. We report a case of multifocal acute cerebral infarctions from meningovascular neurosyphillis in which HR-VWI was instrumental in leading to the etiological diagnosis. A 32-year-old man with history of untreated HIV and polysubstance abuse presented with sudden onset vertigo. CT angiogram of the head and neck showed non-dominant left extracranial vertebral artery occlusion in the V1 segment, and multifocal areas of stenoses in V2 through V4 segments. Non-contrast brain MRI demonstrated multiple small acute infarcts in the left cerebellum, left brachium pontis, medulla and occipital lobe. Rapid plasma reagin was reactive. 3D whole-brain HR-VWI revealed concentric vessel wall contrast enhancement in the left V4 segment, suggestive of inflammation. This HR-VWI finding prompted further investigation with cerebrospinal fluid analysis that revealed reactive fluorescent treponemal antibody absorption test. The patient received high-dose intravenous Penicillin G, was restarted on highly active antiretroviral therapy, and remained neurologically stable to-date. With high spatial resolution and signal-to-noise ratio, HR-VWI allows for visualization of vessel wall inflammation in co-morbid HIV and neurosyphilis.

Concussion and persistent postconcussive symptoms (PPCS) are encountered by clinicians in sports medicine, pediatrics, neurology, physiatry, emergency medicine, and primary care. Clinical management may require a multidisciplinary approach. This article presents a structured method for the diagnosis of concussion and PPCS in the outpatient setting, which includes a history, physical examination, and additional tests as clinically indicated to help identify underlying symptom generators. Treatment for concussion and PPCS should be individualized, based on predominant signs and symptoms, and can include subsymptom threshold aerobic exercise, cervical physical therapy, vestibulo-ocular rehabilitation, behavioral and cognitive psychotherapy, and some symptom-specific pharmacological therapies.

Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.

This article presents a brief history and literature review of chronic traumatic encephalopathy (CTE) in professional athletes that played contact sports. The hypothesis that CTE results from concussion or sub-concussive blows is based largely on several case series investigations with considerable bias. Evidence of CTE in its clinical presentation has not been generally noted in studies of living retired athletes. However, these studies also demonstrated limitation in research methodology. This paper aims to present a balanced perspective amidst a politically charged subject matter.

Background and Study Aims Bowel wall thickening (BWT) on computed tomography (CT) has been frequently reported by radiologists. There are no clear guidelines regarding the level of thickening that is correlated with definite pathology. Radiologists usually rely on their overall subjective impression, and studies on inter-observer agreement (IOA) are lacking. This study evaluated IOA concerning BWT found on abdominal CT and identified the corresponding findings on endoscopy. Patients and Methods Reports of abdominal CTs performed between January 2000 and December 2015 containing the term ‘thickening’ were retrieved from the radiology department database. Corresponding patients who later underwent endoscopy were included. IOA concerning BWT was evaluated using a randomly mixed sample of 80 patients with normal findings or pathological BWT on endoscopy. A search for predictive factors for the subsequent finding of malignancy on endoscopy was performed using multivariate analysis. Results During the study period, 6142 CT scans described thickening, equivalent to a BWT prevalence of 13.7%. Ninety-one patients (mean age, 58 years) were included in the analysis. Thickening was found most commonly in the stomach (38.5%), followed by the rectum (22%) and small intestine (14%). Twenty-seven patients (29.7%) exhibited diffuse BWT, whereas 64 patients showed localised BWT (70.3%). Biopsy was performed for 64 of 91 patients with endoscopies. Among these patients, 8.8% exhibited normal findings, whereas inflammation and malignancy were discovered in 25 and 51.6% of patients, respectively, with a positive predictive value for malignancy of 0.36. The IOA concerning CT for predicting significantly pathological BWT was moderate (mean κ = 0.6). A strong association was evident between the presence of lymph nodes on CT and the presence of neoplastic lesions. Conclusion Our study strongly recommends endoscopic follow-up of patients exhibiting BWT irrespective of the thickening location, especially if it is associated with lymphadenopathy. IOA between radiologists was moderate.

Graphical abstract, Highlights • Gestational gigantomastia presents in early pregnancy as huge continuous breast size enlargement. • Axillary involvement is not mentioned in medical literature before. • Conservative management of Gestational gigantomastia is a valid option depending on patient condition and tolerance., Background Gestational gigantomastia presents in pregnancy as a rapid and excessive enlargement of the breast reducing the quality of life and causing psychological and physical impairment. Huge axillary enlargement due to Gestational gigantomastia is not mentioned in the literature before. Best treatment remains unclear as conservative and medical management are options beside the more aggressive surgical treatment. Case presentation This is a special case of Gestational gigantomastia presented by huge axillary and breast enlargement in a 34-year-old female. Treated successfully in a conservative manner, a near complete spontaneous resolution happened two months post-delivery. Conclusion Axillary involvement is not mentioned in the limited literature discussing the rare disease of gestational gigantomastia. Not only breast but also axillary area can be involved and enlarge due to this disease. Conservative non-operative management was successful.

Highlights • To the best of our knowledge, the current report is the first to mention Sub-pectoral breast primary phyllodes tumor. • Phyllodes tumors usually present in 35–55 years old female patients but should be suspected in any fast-growing breast mass, even in young age groups. • In this case the patient preferred adjuvant radiotherapy to the nipple-areola complex and surrounding skin instead of surgical excision although results are oncologically inferior. • Early diagnosis and initiation of appropriate treatment of Phyllodes tumors may lead to prevent metastasis and improve outcomes., Introduction Phyllodes tumors are rare fibroepithelial breast tumors, accounting for less than 1% of all breast tumors. Most Phyllodes tumors are benign. However, about 10% are malignant. The Mean age of presentation for the Malignant Phyllodes tumors is 40 years. This case report describes an unusual presentation of Phyllodes tumor in a young female with an unusual site and presentation of the tumor. Presentation of case A 23-year-old female presented with multiple left breast rapidly growing masses. Imaging showed two intra-parenchymal left breast masses and one mass lying posterior to the left pectoralis major muscle, anterior to the chest wall. Diagnosed as phyllodes tumor. Nipple areola sparing mastectomy was performed with excision of the tumor and immediate reconstruction using a silicone implant, followed by radiotherapy. Conclusion Phyllodes tumor usually presents in patients between 35–55 years old as a single breast mass. Yet, in rare cases, multifocal disease can happen, and disease can present in younger ages. The sub-pectoral presentation of phyllodes tumor is not mentioned in the literature before this case.

OBJECTIVE: To compare a sample of adolescents with sport-related concussion (SRC) who were prescribed rest with 2 arms of a randomized controlled trial comparing aerobic exercise with placebo-like stretching. We also compared sex differences across the 3 approaches to treatment. DESIGN: Quasi-experimental trial. SETTING: University concussion management clinics. PARTICIPANTS: Adolescent athletes (aged 13-18 years) presenting within 10 days of SRC (mean, 5 days after injury) received a recommendation for rest (rest group [RG], n=48, 15.4±1y, 25% female). Their outcomes were compared with matched samples of adolescents assigned to aerobic exercise (exercise group [EG], n=52, 15.3±2y, 46% female) or placebo-like stretching (placebo group [PG], n=51, 15.4±2y, 47% female) (N=151). MAIN OUTCOME MEASURES: The primary outcome was median days from injury to recovery. The secondary outcome was proportion classified as normal recovery (

Concussive brain injury (CBI) is encountered by clinicians in sports medicine, pediatrics, neurosurgery, neurology, physiatry, and primary care. There is no gold standard diagnostic test for CBI, nor is there consensus on what neuromusculoskeletal physical examination tests should be performed on patients who have sustained CBI. This article presents an approach to the history and physical examination of the patient who has sustained a CBI that is based on a review of the literature evidence and the authors' extensive experience with this patient population. Suggested components include an elemental neurological examination that emphasizes the oculomotor/ophthalmologic and vestibular systems, as well as appropriate musculoskeletal assessment of the craniocervical and upper shoulder girdle complex. The use of supplementary tests for CBI, including assessment of exercise tolerance using the Buffalo Concussion Treadmill Test and tests of neurocognitive function, can aid in the differential diagnosis of CBI. The proposed protocol is envisioned for initial and follow-up assessments in the clinic after CBI, as well as for those with more protracted signs or symptoms. If symptoms persist beyond 2 weeks in adults or 4 weeks in adolescents, then referral to a multidisciplinary center that focuses on CBI is recommended.

Purpose of review Concussion is a complex injury that may present as a variety of clinical profiles, which can overlap and reinforce one another. This review summarizes the medical management of patients with concussion and persistent post-concussive symptoms (PPCS). Recent findings Management of concussion and PPCS relies on identifying underlying symptom generators. Treatment options include sub-symptom threshold aerobic exercise, cervical physical therapy, vestibular therapy, vision therapy, cognitive rehabilitation, cognitive behavioral therapy, pharmacological management, or a combination of treatments. Evidence-based treatments have emerged to treat post-concussion symptom generators for sport-related concussion and for patients with PPCS.

Purpose of review Concussion produces a variety of signs and symptoms. Most patients recover within 2-4 weeks, but a significant minority experiences persistent post-concussive symptoms (PPCS), some of which may be from associated cervical or persistent neurologic sub-system (e.g., vestibular) dysfunction. This review provides evidence-based information for a pertinent history and physical examination of patients with concussion. Recent findings The differential diagnosis of PPCS is based on the mechanism of injury, a thorough medical history and concussion-pertinent neurological and cervical physical examinations. The concussion physical examination focuses on elements of autonomic function, oculomotor and vestibular function, and the cervical spine. Abnormalities identified on physical examination can inform specific forms of rehabilitation to help speed recovery. Emerging data show that there are specific symptom generators after concussion that can be identified by a thorough history, a pertinent physical examination, and adjunct tests when indicated.

Background: Spindle cell carcinoma (SpCC) is an unusual form of squamous cell carcinoma (SCC) and can sometimes present in the breast. Owing to the rarity of breast SpCC, few case studies are available nowadays and proper evidence is scarce. Case presentation: We herein report a 60-year-old female patient, who was referred to the surgery services after presenting with a right breast ulcerated mass. On physical examination, a 7x7 cm mass was found along with a 3 cm ulcer on the top of it. Both mammography and ultrasound showed a dense mass, and tru-cut and skin punch biopsies confirmed neoplastic spindle cells within the lesion. The patient underwent a right total mastectomy with sentinel lymph node biopsies with no further chemotherapy or radiotherapy. Conclusion: Owing to the heterogeneity of SpCC, there is no exact treatment protocol for this type of cancer, and mastectomy or conservative surgery can be performed in certain groups of patients depending on tumor size, stage, and lymph node involvement. Fortunately, promising medical and biological therapies might be of use in the near future.

Rhesus macaques are considered an important reservoir of different gastrointestinal (GI) zoonotic parasites affecting livestock and humans. Loads of GI parasites in the free-ranging rhesus macaques living in close proximity to communities in Bangladesh are still unknown. To estimate the prevalence and diversity of zoonotic GI parasites in rhesus macaques of Bangladesh, a total of 182 freshly voided fecal samples were collected from macaques living in rural (N = 67), peri-urban (N = 57), urban (N = 28), and Safari park (N = 30) between October 2015 and December 2016. All samples were tested by direct smear, sedimentation, flotation, and the McMaster techniques. A total of fourteen different taxa of GI parasites were detected, revealing an overall prevalence of 54.4% (n = 99; 95% confidence interval [CI]: 46.9-61.8). The prevalence of GI parasites was found to be significantly correlated with the mean parasitic taxa per individual in a group (r = 0.90; p = 0.002). The multivariable logistic regression analysis showed that the overall prevalence of GI parasites in macaques was significantly higher in those inhabiting rural areas (62.69%; odds ratio [OR]: 7.22; p = 0.001) and in macaques with interactions with other animals (60.98%; OR: 5.49; p = 0.005). Our results also indicated that the prevalence of Strongyloides spp. and Balantidium coli infections varied significantly between land gradients. Our results also indicate that macaques frequently visit human settlements for food and are found interacting with domestic animals. In conclusion, the high prevalence of zoonotic GI parasite infection in rhesus macaques found in our study may pose a significant public health risk to communities, particularly in rural areas of Bangladesh. Health promotion to at-risk communities focusing on limiting contact with rhesus macaques is necessary to mitigate potential zoonotic transmission.

Context Sport-related concussions (SRC) are common in student athletes. However, current literature suggests that many athletes do not accurately report their symptoms. The under-reporting of concussion symptoms can result in an increased risk of further injury and an underestimation of concussion prevalence. Objective This study aims to identify perspectives on concussion reporting behaviors in student athletes across levels of contact and by sex. Design Cross-sectional study. Setting Elementary and high school, college. Patients or other participants: 1126 female (52%) and male (48%) athletes, mean age 16.6 years. Main outcome measure(s): Standardized questionnaire on concussion reporting during a series of hypothetical scenarios. Results Student athletes participating in sports with higher levels of contact had more education about concussions, yet professed they were less likely to report a concussion. The most common reasons athletes chose not to report were ‘not wanting to miss the game’ and ‘not wanting to let the coach down.’ Minimal differences were found between sexes, with females being just as unlikely, or sometimes more unlikely, to report a concussion than males. Lastly, females playing contact and non-contact sports appear to be more concerned about not wanting to let their coach down than males. Conclusions Although perspective on concussion reporting behavior varied across sports of different levels of contact, we did not find any conclusive evidence of differences in willingness to report a concussion between sexes when compared within the same level of contact.

With the increased worldwide burden of cancer, including aggressive and resistant cancers, oncolytic virotherapy has emerged as a viable therapeutic option. Oncolytic herpes simplex virus (oHSV) can be genetically engineered to target cancer cells while sparing normal cells. This leads to the direct killing of cancer cells and the activation of the host immunity to recognize and attack the tumor. Different variants of oHSV have been developed to optimize its antitumor effects. In this review, we discuss the development of oHSV, its antitumor mechanism of action and the clinical trials that have employed oHSV variants to treat different types of tumor.

Summary Background Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , NCT02387385 . Findings We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretation Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. Funding National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. Translations For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Highlights • Paraduodenal Hernia has rarely been reported in the pediatric age group. • Paraduodenal Hernia is a rare cause of intestinal obstruction and is often misdiagnosed. • CT-scan is the gold standard mean for diagnosis in most cases. • Paraduodenal Hernia must be kept in mind as a possible cause of intestinal obstruction., Introduction Paraduodenal Hernia (PDH) is the most common variant of internal hernia and occurs most often in males during their 4th–6th decades of life. PDH in pediatric age group has rarely been reported in literature with only five cases of age up to 10 years were reported. PDH is a rare cause of intestinal obstruction, which may lead to subsequent strangulation and perforation of the bowel. Presentation of case We reported a 1.5 year-old male child presented with intestinal obstruction. The patient experienced abdominal pain, vomiting and irritability. Abdominal x-ray showed distal intestinal obstruction which was discovered to be a result of left PDH incidentally during the surgery. In addition, we performed a literature search using PubMed to identify the published cases of PDH. We also compared our case with the characteristics of all reported PDHs in toddlers and children up to 10 years of age in a concise table. Discussion Despite its congenital origin, PDH has been reported in childhood age group in very rare occasions rendering the accurate incidence of PDH in infancy and childhood unknown. PDHs can be asymptomatic or can present most commonly with recurrent upper abdominal pain. Diagnosis is quite difficult in the absence of symptoms but could be achieved using a computed tomography (CT-scan) in non-emergency symptomatic patients. Surgical repair is mandatory to avoid potential complications. Conclusion As PDH can lead to major and life threatening complications, it must remain in our minds as a possible cause of intestinal obstruction.

Background: The Buffalo Concussion Treadmill Test (BCTT) is a graded exertion test for assessing exercise tolerance after concussion, but its utility is limited for certain populations. Hypothesis: We developed the Buffalo Concussion Bike Test (BCBT) and tested its comparability with the BCTT. We hypothesize that heart rate (HR) at symptom exacerbation on the BCBT will be equivalent to the BCTT. Study Design: Case-control study. Level of Evidence: Level 3. Methods: Adolescents with acute concussion (AC) (n = 20; mean age, 15.9 ± 1.1 years; 60% male) presenting to a concussion clinic within 10 days of injury and age- and sex-matched healthy controls (n = 20; mean age, 15.9 ± 1.1 years; 60% male) performed the BCTT at first visit and returned within 3 days to perform the BCBT. Test duration, HR, symptom severity (measured using a visual analog scale), and exertion (measured using the Borg Rating of Perceived Exertion) were collected during each test. Results: Adolescents with AC who were exercise intolerant on the BCTT were also intolerant on the BCBT, with symptom exacerbation occurring at a mean 8.1 ± 2.8 minutes on the BCTT versus 14.6 ± 6.0 minutes on the BCBT ( P < 0.01). Two 1-sided t tests showed that the HR at symptom exacerbation in AC patients (137 ± 28 bpm on BCTT vs 135 ± 25 bpm on BCBT; 95% CI, Conclusion: The HR at symptom exacerbation on BCBT is equivalent to the BCTT for the assessment of exercise tolerance after concussion in adolescents. Clinical Relevance: The BCBT can be used in patients with limited mobility or for research interventions that require limited participant motion.

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers., OPCML is a tumour suppressor gene that is epigenetically silenced in ovarian cancer and is somatically mutated in various cancers. Here, the authors solve the X-ray crystal structure of OPCML and model clinically relevant mutations that could contribute to tumorigenesis.

Background and study aim: Baveno VI consensus recommended the use of non- invasive predictors of EV to avoid unnecessary endoscopies. Von Willbrand factor (VWF) and VITRO score, (VWF/ platelet count), are both correlated to liver cirrhosis and fibrosis. The aim of this study was to evaluate the role of VWF and VITRO score as predictors of esophageal varices and their bleeding. Patients and Methods: Seventy seven patients were included in this study. They were randomly selected from cirrhotic patients admitted to endoscopy unit for the first time. They were allocated into two groups;group I:patients who have esophageal varices,group II:patients with no esophageal varices. Results: VWF Ag and VITRO score were significantly higher in the varices group (group I). VWF Ag level was 169.3±20.2 in group I vs 146.8±35.5 µg/dL in group II p

BACKGROUND Intraosseous cavernous skull hemangiomas are rare benign vascular tumors that are usually found incidentally on imaging, with an asymptomatic and slow-growing course. We present a case in which the patient had a mass on her forehead for many years, which began to grow rapidly after head trauma. Imaging characteristics play a crucial role in the diagnosis and description of this disease, and in differentiating it from other more common calvarial lesions that may present with a similar clinical picture. Here, we report an unusual presentation of a large skull hemangioma and discuss the different radiologic imaging findings and pathologic correlations. CASE REPORT A 58-year-old female with history of a lump on her forehead since childhood, which began to grow rapidly after experiencing a closed-head injury. Due to its large size, she went on to seek further management. Radiologic images revealed a frontal skull lesion suggestive of an intraosseous hemangioma. She underwent embolization of the tumor, and 2 days later underwent bilateral frontal craniectomy and cranioplasty. Histopathologic findings confirmed this diagnosis. CONCLUSIONS Intraosseous skull hemangioma may be confidently diagnosed and differentiated from other skull lesions by its imaging characteristics. An accurate diagnosis is essential to selecting correct management and avoiding complications.

Polyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced Th17 program and inefficient Th17 cell differentiation. However, Stat3, but not RORγt, has decreased polyubiquitination, as well as diminished tyrosine-705 activating phosphorylation. Additionally, non-degradative polyubiquitination of Malt1, critical for NF-κB activation and Th17 cell function, is reduced. Mechanistically, Hectd3 promotes K27-linked and K29-linked polyubiquitin chains on Malt1, and K27-linked polyubiquitin chains on Stat3. Moreover, Stat3 K180 and Malt1 K648 are targeted by Hectd3 for non-degradative polyubiquitination to mediate robust generation of RORγt+IL-17Ahi effector CD4+ T cells. Thus, our studies delineate a mechanism connecting signaling related polyubiquitination of Malt1 and Stat3, leading to NF-kB activation and RORγt expression, to pathogenic Th17 cell function in EAE., Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

Background The role of postoperative day 1 drain fluid amylase level in predicting clinically relevant postoperative pancreatic fistula is under investigation. In a previous multicenter study conducted on 338 patients undergoing distal pancreatectomy, day 1 drain fluid amylase level has been correlated to the development of a clinically relevant pancreatic fistula and an amylase value of 2,000 U/L was found to be most predictive of the development of clinically relevant postoperative pancreatic fistula. Our objective was to validate the previously established cutoff level for drain fluid amylase on postoperative day 1 after distal pancreatectomy as a predictor for clinically relevant postoperative pancreatic fistula using a different patient population from the National Surgery Quality Improvement Program database. Methods We studied all patients undergoing distal pancreatectomy from the National Surgery Quality Improvement Program pancreatectomy specific participant use file from 2014 to 2016. We applied the day 1 drain fluid amylase level of 2,000 U/L cutoff to divide patients into 2 groups and compared clinical outcomes in both groups. Among patients with a day 1 drain fluid amylase level Results A total of 1,007 patients underwent distal pancreatectomy. The mean day 1 drain fluid amylase level was 4,290.04 ± 8,492.35 U/L. Clinically relevant postoperative pancreatic fistula occurred in 203 patients (20.2%). Using bivariate analysis, patients with day 1 drain fluid amylase level ≥ 2,000 U/L were more likely to develop clinically relevant postoperative pancreatic fistula (32.5% vs 11.25%, P Conclusion Using a different population of patients and a different data set as well as an independent analysis, we successfully validated a day 1 drain fluid amylase level of 2,000 U/L as striking the best balance in terms of sensitivity and specificity for the detection of clinically relevant postoperative pancreatic fistula. The identified cutoff might be employed in the design of a trial of early drain removal in patients undergoing distal pancreatectomy.

Congenital infantile sarcoma is a rare tumor. Any part of the body can be affected, but upper and lower extremities are common sites of the disease. Diagnosis is reached by clinical presentation, radiological findings, immunohistochemical evaluation and molecular detection of chromosomal abnormality associated with the disease. Differential diagnosis depends on tumor location. Surgical excision is the treatment of choice. Chemotherapy can be of value when complete surgical resection is not possible. Radiotherapy role is limited and needs further evaluation. Here we present a case of huge congenital infantile sarcoma. To the best of our knowledge, this is the first case in literature reporting congenital infantile sarcoma arising from the abdominal wall.

The novel Corona virus disease 2019 (COVID-19) first presented in Wuhan, China. The virus was able to spread throughout the world, causing a global health crisis. The virus spread widely in Jordan after a wedding party held in northern Jordan. In most cases of COVID-19 infection, respiratory symptoms are predominant. However, in rare cases the disease may present with non-respiratory symptoms. The presentation of COVID-19 as a case of intussusception in children is a strange and rare phenomenon. We present here a case of a two-and-a-half month old male baby who was brought to hospital due to fever, frequent vomiting, dehydration and blood in stool. He was diagnosed as intussusception. The child was tested for corona due to the large societal spread of the virus and because he was near his mother, who was suffering from symptoms similar to corona or seasonal flu (she did not conduct a corona test). Patient was treated without surgery and recovered quickly. The COVID-19 infection was without respiratory symptoms, and there was no need for the child to remain in hospital after treatment of intussusception. The relationship between viruses, mesenteric lymphoid hyperplasia, and intussusception is a confirmed relation. ACE2 is the key receptor required for SARA-COV-2 to enter the host cells. ACE2 has been also found in the brush border of the intestinal mucosa, as well as it is a key inflammatory regulator in the intestine. This may suggest that SARSA-COV-2 could invade the respiratory tract as well as gastrointestinal tract or both. Few case reports documented the presentation of COVID-19 as intussusception in children. In the light of the wide-spread of corona virus, performing COVID-19 tests for children with intussusception can help linking the two entities. Development of gastrointestinal symptoms in COVID-19 positive children should raise concern about the development of intussusception.

BACKGROUND Myocardial infarction in nonobstructive coronary artery disease (MINOCA) is a recently described infarct subtype. There are few studies that examine coronary artery disease (CAD) extent, MI size and type, and treatment differences at hospital discharge compared to myocardial infarction in obstructive coronary artery disease (MICAD), or that explore sex-specific MINOCA attributes of coronary anatomy and infarct size. METHODS Our study population consisted of a single tertiary-center of consecutive patients that had coronary angiography for acute MI between 2005 and 2015. The MI type at presentation, MI size and ejection fraction (post-MI), and gender differences between MINOCA patients were examined. RESULT Among 1698 cases with acute MI, 95 had MINOCA (5.6%). MINOCA patients were younger, more often had NSTEMI, lower peak cardiac troponin (cTn) values, and greater ejection fraction than MICAD patients (all P-values

OBJECTIVE To describe the derivation of a brief but pertinent physical examination (PE) for adolescents who have sustained sport-related concussion (SRC). DESIGN Prospective cohort. SETTING University concussion management clinic. PARTICIPANTS Acutely concussed (AC, n = 52, 15.5 ± 1.4 years, 4.4 ± 2 days since injury, 26.2 ± 38 days to recovery, 71% males) and healthy control (HC) adolescents (n = 30, 15.8 ± 1.4 years, 73% males). INTERVENTION Acutely concussed had a PE on visit 1 and were retested at visit 2 (13.6 ± 1 day after visit 1). Acutely concussed were further characterized as normal recovery (NR, n = 41, 15.5 ± 1.5 years, recovery time 13.0 ± 7 days) and delayed recovery (DR, n = 11, 15.5 ± 1.2 years, recovery time 75.4 ± 63 days). MAIN OUTCOME MEASURE Physical examination findings, including cervical, vestibular, and oculomotor systems. RESULTS Visit 1 abnormal PE signs were significantly greater in AC versus HC (2.79 ± 2.13 vs 0.07 ± 0.37, P < 0.0001) but not in NR versus DR (2.61 ± 2.2 vs 3.45 ± 1.8, P = 0.246). Visit 2 abnormal PE signs differentiated NR versus DR (0.17 ± 0.7 vs 2.45 ± 2.1, P < 0.0001). CONCLUSIONS A brief focused PE can help to diagnose SRC, establish recovery, and may have prognostic value.

The number of anticancer agents that have been developed has increased dramatically in the last few decades. However, due to their severe toxicity, high production cost, and low patient compliance, the development of alternative antitumour approaches is urgently needed to minimize these limitations. Several synthetic nanoparticles (NPs), such as polymers, liposomes, dendrimers, and inorganic NPs, have been used in cancer therapy to deliver different chemotherapeutics to the targeted cancer tissue. This approach can enhance the permeability and bioavailability of anticancer agents while reducing the required dose and hence the associated side effects. Microbial NPs have received much attention due to their natural sources, sustainability, minimal cytotoxicity, and low production cost. A considerable number of studies have described the role of microbial NPs as anticancer agents, as well as bioinspired nanomaterials that can be used for cancer theranostics. Despite the promising features of microbial NP applications in cancer treatment, different challenges still need to be addressed. In this chapter, the roles of various microorganisms in the biosynthesis of anticancer agents, biosensing agents, and metallic NPs for cancer applications are explored. Moreover, the use of genetically engineered microbes as nanocarriers for anticancer molecules is discussed. Finally, the main challenges of microbial NPs as an alternative strategy for cancer therapy are highlighted.

Objectives To identify predictors of prolonged recovery (ie, >28 days) using patient demographic factors and healthy, norm-based cutoffs on a multimodal test battery in adolescents after sport-related concussions (SRCs). Design Retrospective cohort. Patients were deemed recovered after successful completion of return-to-play/school protocols and received medical clearance. Setting Community concussion clinic. Patients Male and female adolescent student athletes diagnosed with a SRC and evaluated within 1 week of injury. Independent variables Patient demographics, medical history, injury description, computerized neurocognitive testing, vestibular/ocular testing, and symptoms at initial clinical visit. Main outcome measures Performance on clinical testing to predict recovery duration, classified as normal ( 28 days). Results A total of 201 adolescent student athletes (age = 15.3 ± 1.4 years) were included (female 35%). Average recovery duration for the entire cohort was 22.3 ± 13.3 days, with 22% (n = 45) of adolescent student athletes taking >28 days to recover. The final model was 88.3% accurate in classifying normal and prolonged recovery. Predictor variables included sex, loss of consciousness, history of ocular disorder, history of concussion, performance on visual motor speed composite, visual motion sensitivity symptom provocation and near point of convergence distance, number-naming total time, and symptom count. Conclusions These findings suggest that using norm-based cutoffs from cognitive, oculomotor, and vestibulo-ocular testing and symptom reporting, clinicians can accurately predict a prolonged recovery (sensitivity = 81%) and normal recovery (specificity = 83%) in an adolescent, SRC cohort.

Context: Emerging research supports the use of mild to moderate aerobic exercise for treating sport-related concussion (SRC) and persistent postconcussive symptoms (PPCS), yet the current standard of care remains to be strict rest. The purpose of this review is to summarize the existing literature on physical activity and prescribed exercise for SRC and PPCS. Evidence Acquisition: PubMed and Embase were searched in April of 2019 for studies assessing rest or prescribed exercise for SRC and PPCS. No specific search syntax was used. Study Design: Clinical review. Level of Evidence: Level 4. Results: A majority of studies show that spontaneous physical activity is safe after SRC and that subsymptom threshold aerobic exercise safely speeds up recovery after SRC and reduces symptoms in those with PPCS. Exercise tolerance can safely be assessed using graded exertion test protocols within days of injury, and the degree of early exercise tolerance has diagnostic and prognostic value. Conclusion: Subsymptom threshold aerobic exercise is safe and effective for the treatment of SRC as well as in athletes with PPCS. Further research is warranted to establish the most effective method and dose of aerobic exercise for the active treatment of SRC and whether early exercise treatment can prevent PPCS in athletes. Strength of Recommendation Taxonomy: 2.

Background Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance. Methods This case‐control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4‐7, 8‐14, 15‐30, and 31‐60 days post‐mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi‐interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. Results A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross‐validated area under the curve (AUC) of .857 in the training set (95% CI, .816‐.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post‐Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross‐validated AUC of .835 (95% CI, .782‐.880) and .853 (95% CI, .803‐.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845‐.925) as symptom burden and four ncRNAs (.932; 95% CI, .890‐.965). Conclusion Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI., Levels of nine salivary noncoding RNAs (ncRNAs) accurately differentiated 251 individuals with mild traumatic brain injury (mTBI) from 287 peers with mTBI‐like symptoms. ncRNA performance (area under the curve [AUC] = .857) was similar to other diagnostic adjuncts: neurocognition (AUC = .835) and balance (AUC = .853). Combining ncRNA levels with symptom severity (AUC = .932) demonstrated comparable accuracy to current clinical guidelines (symptom severity plus neurocognition; AUC = .888).

Background Cytochromes P450 (CYPs) constitute an enzyme family involved in the oxidative metabolism of a wide variety of endogenous and exogenous compounds, including anti-cancer drugs and carcinogens. Unlike other human CYPs, CYP4Z1 is highly expressed in human breast carcinoma and is associated with poor prognosis. As a result, CYP4Z1 was hypothesised to be a potential biomarker or drug target for the discovery and development of promising anti-cancer therapies. Materials and methods CYP4Z1 expression was immunohistochemically studied in a set of 100 different human tissues, including normal, benign, malignant and metastatic tissues, which originated from 27 anatomical sites. As a tumour model for CYP4Z1 expression, a panel of different breast cancers was evaluated for CYP4Z1 expression and its relation to histopathological features and prognostic immunohistochemical markers. Results The immunohistochemical results revealed that CYP4Z1 was expressed in only one (4.3%) of the normal tissues from the mammary glands, while the expression of the enzyme was positive in 1 (11%), 12 (19%) and 2 (40%) of the benign, malignant and metastatic tissues, respectively. Interestingly, several tumour entities showed prominent expressions of CYP4Z1, including carcinomas of adrenal cortex, squamous cells of oesophagus, lung and cervix, as well as seminoma, astrocytoma, melanoma and lastly endometrial adenocarcinoma. In breast cancers, CYP4Z1 was expressed in 82% of the cases. Its expression was significantly associated with the pathology of tumour, histological grade and status of lymph node metastasis. Importantly, it was also significantly associated with the expressions of Her2, P53 and Ki-67. Conclusion These findings greatly support future plans for the use of CYP4Z1 as a biomarker or target for anti-cancer drugs. However, large-scale validation studies are needed to better delineate the potential use of CYP4Z1 for therapeutic purposes.

Cystic Fibrosis (CF), an autosomal recessive genetic disease, is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation reduces the release of chloride ions (Cl−) in epithelial tissues, and hyperactivates the epithelial sodium channels (ENaC) which aid in the absorption of sodium ions (Na+). Consequently, the mucus becomes dehydrated and thickened, making it a suitable medium for microbial growth. CF causes several chronic lung complications like thickened mucus, bacterial infection and inflammation, progressive loss of lung function, and ultimately, death. Until recently, the standard of clinical care in CF treatment had focused on preventing and treating the disease complications. In this review, we have summarized the current knowledge on CF pathogenesis and provided an outlook on the current therapeutic approaches relevant to CF (i.e., CFTR modulators and ENaC inhibitors). The enormous potential in targeting bacterial biofilms using antibiofilm peptides, and the innovative therapeutic strategies in using the CRISPR/Cas approach as a gene-editing tool to repair the CFTR mutation have been reviewed. Finally, we have discussed the wide range of drug delivery systems available, particularly non-viral vectors, and the optimal properties of nanocarriers which are essential for successful drug delivery to the lungs.

The use of biological agents for the treatment of chronic inflammatory conditions such as inflammatory bowel diseases (IBD) has been on the rise.1,2 Current biological therapies include antitumor necrosis factor-α (anti-TNF-α), anti-interleukin-12/23, and anti-integrin agents. Before initiation of biological drugs, screening for Mycobacterium tuberculosis infection is required to avoid reactivation or worsening of disease after immunosuppression. It has been shown that anti-TNF-α treated patients have a 14-fold increased risk of tuberculosis (TB) infection/reactivation compared with healthy controls.3 The methods for screening for TB have evolved over time and vary from region to region.

Context The King-Devick (KD) test is a rapid number-reading test that has emerging use in the assessment of sport-related concussion (SRC). Previous research suggested that healthy individuals and patients with acute concussions who had shorter recovery times ( Objective To assess if the absence of postexertional improvement on the KD test within 10 days of concussive head injury was associated with a longer duration of recovery. Design Prospective cohort study. Setting University concussion-management clinics. Patients or Other Participants Male and female adolescent athletes (n = 99, aged 13–18 years) presenting within 10 days of SRC. Main Outcome Measure(s) The KD test was administered before and after the Buffalo Concussion Treadmill Test (BCTT). Days from injury to recovery, with recovery defined as being asymptomatic, confirmed by the assessment of a physician who was blinded to the treatment group, and the return of normal exercise tolerance on the BCTT were recorded. Results Participants with postexertional slowing (PES group, n = 33) had a longer duration of recovery (17 days versus 13.5 days, P = .033) than participants without PES (no-PES group, n = 66). At any clinic visit, PES was also associated with a relative risk of 2.36 (95% confidence interval = 1.55, 3.61; P < .001) of not recovering within the following week. Conclusions The current study validates our prior work showing that acutely concussed adolescents who did not display the typical learning effect on the KD test after the BCTT took longer to recover from SRC than those who exhibited the typical learning effect.

Systemic lupus erythematosus (SLE) is an autoimmune disease and can be associated with other autoimmune diseases. SLE usually presents with skin change and rarely presents with gangrene. SLE gangrene usually involves the digits of upper extremities. We report the first case of SLE associated with an extremely rare constellation of neuromyelitis Optica (NMO) and diabetes mellitus type 1, presented with a rare form of the SLE gangrene which involves bilateral lower extremities up to midlegs, a case that has not yet been reported in the literature. Although SLE gangrene may respond to immunosuppressants, it has a high risk of complications that can end up with amputations.

Introduction: The Baveno VI consensus recommended the use of noninvasive predictors to identify patients at high risk of esophageal varices (EV) in whom endoscopic evaluation is most needed. Kallistatin is a protein molecule synthesized by the liver, and its level declines with the deterioration of liver functions. We aim to explore the role of kallistatin as a predictor of esophageal varices. Methods: This case–control study included 70 cirrhotic patients (35 patients with EV and 35 patients without EV). The laboratory investigations and upper GI endoscopy were performed, and the serum kallistatin level was measured in all patients. Results: The mean level of serum kallistatin was significantly lower in patients with varices (12.2 ± 5.6 vs 16.9 ± 4.8 μg/ml, p = 0.009). It also shows a significant decline in patients with large varices. Kallistatin can predict the presence of EV and large EV at cut off values of 15.8 and 8.9 μg/ml, respectively, with sensitivity and specificity of 71.4% and 54.3% for EV and 50% and 94.8% for large EV. Discussion: Kallistatin is a promising marker that can be used to predict the presence of esophageal varices especially when they are large and risky.

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.

Objective To provide an overview of 3 studies of the same population of retired professional contact sport athletes compared with age-matched noncontact sport athlete controls on cognition, executive function, behavior, and advanced brain imaging. Setting University Concussion Management Clinic. Participants Twenty-two retired professional hockey and football athletes (average age 56 years) and 21 age-matched noncontact sport athlete controls. Design Case control. Main measures Participants were assessed on a broad range of neuropsychological measures that are associated with identification of mild cognitive impairment and executive function. Athletes were also assessed using self-report measures of executive function and personality. Advanced structural and functional imaging techniques were utilized as well. Results The former National Football League and National Hockey League athletes perceived themselves to have impaired executive function, but this was not confirmed by objective neurocognitive assessment. No significant differences were found when comparing contact-sport athletes with controls on the presence of mild cognitive impairment or brain structural and functional tissue injury. Contact sport athletes were more anxious and more likely to report unusual beliefs and experiences. Conclusion None of the retired contact sport athletes qualified as having early-onset dementia consistent with chronic traumatic encephalopathy. There were no remarkable differences in imaging, cognition, behavior, or executive function from noncontact sport athletes. The results underscore an apparent disconnect between public perceptions and evidence-based conclusions about the inevitability of chronic traumatic encephalopathy and the potential neurodegenerative effect on former athletes from contact sports.

Hearing loss is the most prevalent sensory disability worldwide and may be caused by age, drugs or exposure to excessive noise. We have previously developed a minimally-invasive nanohydrogel drug delivery system that successfully delivers nanoparticles into the inner ear. We have substantially extended this technique by functionalizing the nanoparticles and introducing a targeting peptide which recognizes prestin, a transmembrane electromotile protein uniquely expressed in outer hair cells (OHCs) of the inner ear. We demonstrate the successful delivery of molecules and plasmids specifically to OHCs. When compared to untargeted nanoparticles, the delivery of a c-Jun N-terminal kinase (JNK) inhibitor, D-JNKi-1, to OHCs by targeted nanoparticles improved protection from noise induced hearing loss (NIHL). This is the first demonstration of a protection from NIHL using a novel safe and controllable delivery system which is minimally-invasive to the inner ear and, as such, is an extremely appealing technique for use in many clinical applications.

OBJECTIVE: Intra-cranial pressure (ICP) after mild traumatic brain injury (mTBI) is poorly studied due to lack of sensitive non-invasive methods. The purpose of this review was to summarize the existing knowledge of changes in ICP after mTBI. LITERATURE SELECTION: PubMed, Embase, CINAHL, and Scopus were searched by 3 reviewers independently up to December 2016. Inclusion criteria: animal and human studies measuring ICP and brain oedema after an mTBI. Exclusion criteria: Moderate and severe forms of traumatic brain injury, repeat samples, and studies that measured ICP at the time of impact but not after. Study quality was assessed using Downs and Black criteria. RESULTS: Of 1067 papers, 9 studies were included. In human studies, 1 provided direct evidence on increased, 1 provided indirect evidence of increased, and 2 provided indirect evidence of decreased ICP. In animal studies, 3 studies provided direct evidence of increased, 1 provided indirect evidence of increased, and 1 provided indirect evidence of no change in ICP. CONCLUSION: The existing research suggests that there may be increased ICP after mTBI and animal studies suggest an elevation for days which returns to baseline, which corresponds with functional and symptomatic recovery. Future human studies using sensitive indirect methods to measure ICP longitudinally after mTBI are needed.

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles’ ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.