Arthropod Bites and Stings.

Arthropods, including insects and arachnids, significantly affect humans as vectors for infectious diseases. Arthropod bites and stings commonly cause minor, usually self-limited reactions; however, some species are associated with more severe complications. Spider bites are rarely life-threatening. There are two medically relevant spiders in the United States. Widow spider (Latrodectus) envenomation can cause muscle spasm and severe pain that should be treated with analgesics and benzodiazepines. Antivenom is not widely available in the United States but may be considered for severe, refractory cases. Recluse spider (Loxosceles) bites are often overdiagnosed, should be treated supportively, and only rarely cause skin necrosis. Centruroides scorpions are the only medically relevant genus in the United States. Envenomation causes neuromuscular and autonomic dysfunction, which should be treated with analgesics, benzodiazepines, supportive care, and, in severe cases, antivenom. Hymenoptera, specifically bees, wasps, hornets, and fire ants, account for the most arthropod-related deaths in humans, most commonly by severe allergic reactions to envenomation. In severe cases, patients are treated with analgesia, local wound care, and systemic glucocorticoids. Diptera include flies and mosquitoes. The direct effects of their bites are usually minor and treated symptomatically; however, they are vectors for numerous infectious diseases. Arthropod bite and sting prevention strategies include avoiding high-risk areas, covering exposed skin, and wearing permethrin-impregnated clothing. N,N-diethyl- m-toluamide (DEET) 20% to 50% is the most studied and widely recommended insect repellant.

Risk Stratification and Pain Outcomes Following Revision Total Hip Arthroplasty for Adverse Local Tissue Reactions.

BACKGROUND: Revision total hip arthroplasty (THA) for adverse local tissue reactions (ALTRs) secondary to head-neck taper corrosion is associated with a high complication rate. Diagnosis of ALTR is based on risk stratification using the patient's history and examination, implant risk, serum metal ion levels, and imaging. The purpose of this study was to determine if stratification using similar risk factors is predictive of outcomes following revision THA for metal-on-polyethylene (MoP) ALTR. METHODS: We performed a retrospective review on 141 patients revised for ALTR due to head-neck taper corrosion. Pain outcomes following surgery were analyzed using a generalized linear mixed model. Complications were defined as instability/dislocation, infection, fracture, nerve palsy, leg-length discrepancy, or reoperation. RESULTS: The overall complication rate was 17.7%. The odds of having pain decreased by 44% after revision surgery (Odds Ratio = 0.56, 95% Confidence Interval: 0.324 to 0.952). There was no significant difference in instability/dislocation based on either increased or decreased head-neck offset (P = .67) or magnetic resonance imaging findings of abductor loss, effusion size, and degree of ALTR (P = .73). Increased serum cobalt (P = .31) and chromium (P = .08) levels did not predict complications; however, a decreased cobalt-chromium ratio was associated with postoperative complications (2.8 versus 3.5; P = .002). CONCLUSION: These findings are the first to suggest that patients who have ALTR after MoP THA undergoing revision surgery demonstrated major pain relief. Increasing femoral head offset did not change rates of instability/dislocation. In clinical scenarios where preoperative cobalt-chromium femoral head offsets were greater than available ceramic head offsets, a mandatory decrease in femoral head offset did not increase rates of instability/dislocation.

Comparison of Asymptomatic and Symptomatic Adverse Local Tissue Reaction in Patients With Head-Neck Taper Corrosion.

BACKGROUND: Diagnosis of adverse local tissue reaction (ALTR) in metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper corrosion is challenging. The purpose of this study is to compare differences between asymptomatic and symptomatic ALTR in an observational cohort, including presentation, metal ion differences, and metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) findings. METHODS: We performed a retrospective review of an observational cohort of 492 MoP THA patients at increased risk of developing ALTR. Ninety-four patients underwent revision arthroplasty for ALTR. Patients were stratified into symptomatic and asymptomatic ALTR groups. Presentation, metal ion levels, and imaging findings were compared. RESULTS: For patients with confirmed ALTR, 41% were asymptomatic. There was a statistically significant difference in the serum chromium levels between symptomatic and asymptomatic ALTR patients (2.2 µg/L vs 3.1 µg/L, P = .05). There was no statistically significant difference between the serum cobalt levels or MRI findings in these 2 groups. We observed that extracapsular disease associated with ALTR could be misinterpreted as trochanteric bursitis. CONCLUSION: Almost half of the MoP THA ALTR cases identified were asymptomatic. Cobalt levels could not differentiate between symptomatic and asymptomatic pseudotumor formation. Symptomatic and asymptomatic MoP ALTRs have similar MARS MRI characteristics. Our findings suggest that it is essential to risk stratify patients who could potentially have ALTR based on implant type, symptoms, ion levels, and MARS MRI.

Acute Appendicitis: Efficient Diagnosis and Management.

Appendicitis is one of the most common causes of acute abdominal pain in adults and children, with a lifetime risk of 8.6% in males and 6.7% in females. It is the most common nonobstetric surgical emergency during pregnancy. Findings from the history, physical examination, and laboratory studies aid in the diagnosis of acute appendicitis. Right lower quadrant pain, abdominal rigidity, and periumbilical pain radiating to the right lower quadrant are the best signs for ruling in acute appendicitis in adults. Absent or decreased bowel sounds, a positive psoas sign, a positive obturator sign, and a positive Rovsing sign are most reliable for ruling in acute appendicitis in children. The Alvarado score, Pediatric Appendicitis Score, and Appendicitis Inflammatory Response score incorporate common clinical and laboratory findings to stratify patients as low, moderate, or high risk and can help in making a timely diagnosis. Recommended first-line imaging consists of point-of-care or formal ultrasonography. Appendectomy via open laparotomy or laparoscopy is the standard treatment for acute appendicitis. However, intravenous antibiotics may be considered first-line therapy in selected patients. Pain control with opioids, nonsteroidal anti-inflammatory drugs, and acetaminophen should be a priority and does not result in delayed or unnecessary intervention. Perforation can lead to sepsis and occurs in 17% to 32% of patients with acute appendicitis. Prolonged duration of symptoms before surgical intervention raises the risk. In moderate- to high-risk patients, surgical consultation should be accomplished quickly to reduce morbidity and mortality resulting from perforation.

Treating Painful Diabetic Peripheral Neuropathy: An Update.

Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.

Predicted structure and domain organization of rotavirus capping enzyme and innate immune antagonist VP3.

UNLABELLED: Rotaviruses and orbiviruses are nonturreted Reoviridae members. The rotavirus VP3 protein is a multifunctional capping enzyme and antagonist of the interferon-induced cellular oligoadenylate synthetase-RNase L pathway. Despite mediating important processes, VP3 is the sole protein component of the rotavirus virion whose structure remains unknown. In the current study, we used sequence alignment and homology modeling to identify features common to nonturreted Reoviridae capping enzymes and to predict the domain organization, structure, and active sites of rotavirus VP3. Our results suggest that orbivirus and rotavirus capping enzymes share a domain arrangement similar to that of the bluetongue virus capping enzyme. Sequence alignments revealed conserved motifs and suggested that rotavirus and orbivirus capping enzymes contain a variable N-terminal domain, a central guanine-N7-methyltransferase domain that contains an additional inserted domain, and a C-terminal guanylyltransferase and RNA 5'-triphosphatase domain. Sequence conservation and homology modeling suggested that the insertion in the guanine-N7-methyltransferase domain is a ribose-2'-O-methyltransferase domain for most rotavirus species. Our analyses permitted putative identification of rotavirus VP3 active-site residues, including those that form the ribose-2'-O-methyltransferase catalytic tetrad, interact with S-adenosyl-l-methionine, and contribute to autoguanylation. Previous reports have indicated that group A rotavirus VP3 contains a C-terminal 2H-phosphodiesterase domain that can cleave 2'-5' oligoadenylates, thereby preventing RNase L activation. Our results suggest that a C-terminal phosphodiesterase domain is present in the capping enzymes from two additional rotavirus species. Together, these findings provide insight into a poorly understood area of rotavirus biology and are a springboard for future biochemical and structural studies of VP3. IMPORTANCE: Rotaviruses are an important cause of severe diarrheal disease. The rotavirus VP3 protein caps viral mRNAs and helps combat cellular innate antiviral defenses, but little is known about its structure or enzymatic mechanisms. In this study, we used sequence- and structure-based alignments with related proteins to predict the structure of VP3 and identify enzymatic domains and active sites therein. This work provides insight into the mechanisms of rotavirus transcription and evasion of host innate immune defenses. An improved understanding of these processes may aid our ability to develop rotavirus vaccines and therapeutics.

Options for women with unintended pregnancy.

Unintended pregnancy refers to unwanted, unplanned, or mistimed pregnancies. One-half of all pregnancies in the United States are unintended, and family physicians are often asked to provide counseling, support, and resources for women with unintended pregnancies. Options include carrying the infant to term and raising the child, carrying the infant to term and choosing adoption, or having an induced abortion. Family physicians should be equipped to direct women who choose to raise the infant to appropriate care and resources. Most U.S. women do not choose adoption, but there are multiple resources for women interested in this option. Physicians should not broker adoptions, match potential parents with mothers, or adopt children of their own patients. Induced abortion is performed in the first or second trimester of pregnancy. Medical management is comparable with surgical management, and both methods are safe and effective. Combination regimens with mifepristone and misoprostol are the most effective medical methods. Dilation and curettage and vacuum aspiration are the most common surgical methods.

Acute pericarditis: diagnosis and management.

Acute pericarditis, inflammation of the pericardium, is found in approximately 5% of patients admitted to the emergency department for chest pain unrelated to acute myocardial infarction. It occurs most often in men 20 to 50 years of age. Acute pericarditis has a number of potential etiologies including infection, acute myocardial infarction, medication use, trauma to the thoracic cavity, and systemic diseases, such as rheumatoid arthritis. However, most etiologic evaluations are inconclusive. Patients with acute pericarditis commonly present with acute, sharp, retrosternal chest pain that is relieved by sitting or leaning forward. A pericardial friction rub is found in up to 85% of patients. Classic electrocardiographic changes include widespread concave upward ST-segment elevation without reciprocal T-wave inversions or Q waves. First-line treatment includes nonsteroidal anti-inflammatory drugs and colchicine. Glucocorticoids are traditionally reserved for severe or refractory cases, or in cases when the cause of pericarditis is likely connective tissue disease, autoreactivity, or uremia. Cardiology consultation is recommended for patients with severe disease, those with pericarditis refractory to empiric treatment, and those with unclear etiologies.

Predictors of Adverse Local Tissue Reaction in a High-Risk Population.

BACKGROUND: Adverse local tissue reaction (ALTR) is a recognized complication of total hip arthroplasty (THA) with metal-on-polyethylene (MoP) bearing surface implants. Specific models of THA implants have been identified as having a higher incidence of ALTR. The purpose of this study is to determine if serum metal levels, patient symptoms, implant factors, and imaging findings can be predictive of ALTR within this high-risk population. METHODS: We retrospectively reviewed an observational cohort of 474 patients who underwent MoP THA and were at increased risk of having ALTR. Patients were stratified based on the presence or absence of ALTR. Patient symptoms, serum metal ions, implant head offset, and imaging findings were compared. RESULTS: Patients with ALTR were more likely to be symptomatic (52.9% vs 9.9%, P < .0001). The presence of ALTR was associated with significantly higher serum cobalt and chromium levels (6.2 ppb vs 3.6 ppb, P < .0001; 2.3 ppb vs 1.2 ppb, P < .0001). Head offsets greater than 4 mm were associated with a higher prevalence of ALTR (53% vs 38%, P = .05). On metal artifact reduction sequence magnetic resonance imaging, patients with ALTR had larger effusions (4.7 cm vs 2.1 cm, P < .001) and a higher incidence of trochanteric bursitis (47% vs 16%, P < .001). CONCLUSIONS: In high-risk MoP implants, serum cobalt and chromium levels are elevated, even in patients without ALTR. A larger femoral head offset is a risk factor for the development of ALTR. Our study suggests that patients presenting with painful THA and elevated metal ions require risk stratification based on patient symptoms, metal artifact reduction sequence magnetic resonance imaging findings, and implant factors.

Integrative Medicine: Manual Therapy.

Manual therapy, or manipulative therapy, is performed primarily by osteopathic physicians, chiropractors, and physical therapists to relieve pain and improve function. As safe prescribing of opioids has become a concern and nondrug therapies for pain management are used more widely, manual therapy has become an attractive treatment option for many patients. A variety of techniques are used, including myofascial release, strain-counterstrain, muscle energy, high velocity/low amplitude, Still, and others. The most common conditions for which patients seek manual therapies are back pain, neck pain, and extremity problems. These therapies also are used to manage many other conditions. Studies show that, in general, manual therapies may improve pain and function in the short and moderate term in patients with acute and chronic back pain, neck pain, rotator cuff conditions, and temporomandibular joint disorders. These therapies also are used in patients with sciatica, migraine, carpal tunnel syndrome, pregnancy-related pelvic girdle pain, and infantile colic. Manual therapies may result in improvements in these conditions, but there is no high-quality research to confirm their benefits. Many studies show benefits that are similar to those of other commonly used therapies, or that are not superior to the benefits shown with sham manipulation.

Integrative Medicine: Acupuncture.

Acupuncture is used to manage pain and a variety of medical and psychological conditions. It modulates nociceptive areas of the brain, affects neuropeptide and purinergic signaling, and stimulates production of opioid neuropeptides. There are many types of acupuncture, including traditional, dry needling, laser, auricular, scalp, Japanese, and Korean. There is evidence that traditional acupuncture is effective in the management of many conditions, with strong evidence of benefit for chronic back pain and osteoarthritis-related knee pain. In the United States, the conditions most commonly managed with acupuncture are low back pain, depression, anxiety, headache, and arthritis. There are no absolute contraindications. Relative contraindications include frailty and febrile illness. Acupuncture should not be used in areas of skin infection or breakdown. Acupuncture typically is avoided during the first trimester of pregnancy. Reports of serious adverse effects are rare but include pneumothorax, infection, organ or tissue injuries, and seizures. Serious adverse effects of electroacupuncture (eg, skin burns, pacemaker or implantable cardioverter-defibrillator dysfunction) are limited to case reports. Thirty-three states in the United States consider acupuncture to be within the scope of practice of physicians. Other states require specific acupuncture training. Medicare provides coverage for acupuncture for management of chronic low back pain.

Integrative Medicine: Herbal Supplements.

Various herbal medicines have been used around the world for more than 5,000 years. Herbal medicines, or herbal supplements, are defined as any products originating from plants and used to preserve or recover health. In the United States, the popularity of herbal supplements has increased in the last several decades. Many physicians do not ask patients about herbal supplement use, and one-third of patients do not inform their physician about supplement use. However, physicians should ask, because although many supplements are considered low risk and safe, some have significant risks of adverse effects. For example, St John's wort (Hypericum perforatum) can have significant drug interactions with prescription or over-the-counter drugs. The effectiveness of herbal supplements in the management of specific conditions varies. For some conditions, there is robust clinical data supporting the use of specific herbal supplements, but for other conditions there is poor or insufficient data. The content and safety of herbal supplements are the purview of the Food and Drug Administration (FDA). However, the FDA primarily responds to after-the-fact reports of postmarketing safety concerns. When an herbal supplement-related adverse effect is suspected, patients or physicians should report it to the FDA via the MedWatch reporting system.

Integrative Medicine: Cannabis and Cannabis-Related Drugs.

Cannabis is a genus of flowering herbs in the Cannabaceae family. Federal law defines dried plant material preparations of the subspecies Cannabis sativa as marijuana. The term cannabis refers to all products derived from Cannabis plants. The active compounds in cannabis are cannabinoids, which include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component, whereas CBD has no psychoactive effects. There are three Food and Drug Administration (FDA)-approved cannabis-related drugs. Dronabinol and nabilone (Cesamet) are approved for chemotherapy-induced nausea and vomiting; cannabidiol (Epidiolex) is approved for two pediatric epilepsy syndromes. FDA-approved cannabis-related drugs, marijuana, and cannabis formulations have been studied for the management of other conditions and symptoms (eg, cachexia, chemotherapy-induced nausea and vomiting, chronic pain, muscle spasticity) and have shown varying effectiveness. CBD formulations have been shown to be effective for certain forms of epilepsy. However, marijuana, cannabis-containing products, and cannabis-derived products in general are not approved by the FDA for any indication. Adverse effects include impaired executive function, cognition, and driving. Physicians can recommend use of marijuana under medical marijuana laws but cannot prescribe it, as it is classified as a Schedule I controlled substance. Laws regulating use of marijuana and cannabis products vary among states.

Establishing Normative Values for Inter-Limb Kinetic Symmetry During Landing in Uninjured Adolescent Athletes.

BACKGROUND: Assessment of inter-limb kinetic symmetry during landing could provide valuable insights when working with athletes who have undergone anterior cruciate ligament reconstruction. However, it is difficult to determine if the asymmetry exhibited by an injured athlete is excessive or within a range that is similar to uninjured athletes, until normative values are established. PURPOSE: The purpose of this study was to establish normative values for inter-limb impact force symmetry in uninjured adolescent athletes. In addition, an example is provided of how these normative values could be used to identify athletes who exhibit atypically high levels of asymmetry following anterior cruciate ligament reconstruction. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and thirty-six uninjured athletes completed drop vertical jumps and countermovement jumps while force plates recorded ground reaction forces. Symmetry indices captured inter-limb symmetry in impact forces during landing for both tasks. These symmetry indices were also combined to create an index that captured symmetry across both tasks. Normative values were established using the uninjured athletes' data. Eleven athletes who had undergone anterior cruciate ligament reconstruction and been cleared to return to landing and jumping performed the same tasks and their data were compared to the results for the uninjured group. RESULTS: Measures of central tendency, variability, percentiles, and outliers were calculated/identified based on the uninjured athletes' symmetry indices. Six of the 11 injured athletes exhibited atypically high symmetry index values. CONCLUSION: The normative values established as part of this study may serve as a basis for identifying athletes who exhibit atypically high levels of inter-limb impact force asymmetry during jumping tasks following anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: 3b.

Kinetic Asymmetry During a Repetitive Tuck Jump Task in Athletes with a History of Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Athletes who have undergone anterior cruciate ligament reconstruction typically exhibit relatively high/rapid loading of their uninvolved limb during bilateral landing and jumping (vs. their limb that underwent reconstruction), which may place their uninvolved limb at risk for injury. However, previous studies have only examined forces and loading rates for tasks involving an isolated land-and-jump. PURPOSE: The purpose of this study was to examine bilateral landing and jumping kinetics during performance of a repetitive tuck jump task in athletes who had undergone anterior cruciate ligament reconstruction and completed rehabilitation. STUDY DESIGN: Cross-sectional study. METHODS: Nine athletes (four males, five females) participated in this study. All participants had undergone successful unilateral anterior cruciate ligament reconstruction, had completed post-operative rehabilitation, and were in the process of completing return-to-sport testing. Athletes performed a repetitive tuck jump task for 10 seconds, while ground reaction forces were recorded for their uninvolved and involved limbs via separate force platforms. Two-way analysis of variance, for within-subjects factors of limb and cycle, was performed for the impact forces, loading rates, and propulsive forces from the first five land-and-jump cycles completed. RESULTS: There was not a limb-by-cycle interaction effect or main effect of cycle for the impact forces, loading rates, or propulsive forces; however, there was a main effect of limb for the impact forces (F(1, 8) = 14.64; p=0.005), loading rates (F(1, 8) = 5.60; p=0.046), and propulsive forces (F(1, 8) = 10.38; p=0.012). Impact forces, loading rates, and propulsive forces were higher for the uninvolved limb, compared to the involved limb, over the five land-and-jump cycles analyzed. CONCLUSION: The athletes in this study consistently applied higher and more rapid loads to their uninvolved limb over multiple land-and-jump cycles. This may help to explain the relatively high injury rates for the uninvolved limb in athletes who have returned to sport following anterior cruciate ligament reconstruction.

Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread.

Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring in 74% of 27 biologically malignant tumors but only 10% of 61 clinically benign tumors. The size of the strumal component rather than the overall size of the ovarian teratoma also had some predictive value. Tumors with a strumal component < or =6 cm recurred rarely (7%), whereas 33% of the consult and 88% of the literature cases > or =12 cm were clinically malignant. Except for a papillary pattern or poorly differentiated cancer, no microscopic feature reliably predicted the clinical outcome, including those typically associated with malignancy in primary thyroid tumors. Among the consult cases, 7% with histologic follicular adenomas and 29% with papillary carcinomas were clinically malignant. Unequivocal vascular invasion was rare, precluding assessment of its effect. Optically clear nuclei, when extensive, were useful to diagnose papillary carcinoma, but were present nevertheless in smaller numbers in both macrofollicular and microfollicular adenomas. Eight tumors confined initially to the ovary (stage 1) recurred. Papillary carcinomas recurred earlier (average 4 y) than follicular adenomatous neoplasms (average 11 y, range: 1-29 y). Overall, the survival rate for all patients was 89% at 10 years and 84% at 25 years, indicating the need for routine long-term follow-up.

Testing Quick Response (QR) Codes as an Innovation to Improve Feedback Among Geographically-Separated Clerkship Sites.

BACKGROUND AND OBJECTIVES: Collection of feedback regarding medical student clinical experiences for formative or summative purposes remains a challenge across clinical settings. The purpose of this study was to determine whether the use of a quick response (QR) code-linked online feedback form improves the frequency and efficiency of rater feedback. METHODS: In 2016, we compared paper-based feedback forms, an online feedback form, and a QR code-linked online feedback form at 15 family medicine clerkship sites across the United States. Outcome measures included usability, number of feedback submissions per student, number of unique raters providing feedback, and timeliness of feedback provided to the clerkship director. RESULTS: The feedback method was significantly associated with usability, with QR code scoring the highest, and paper second. Accessing feedback via QR code was associated with the shortest time to prepare feedback. Across four rotations, separate repeated measures analyses of variance showed no effect of feedback system on the number of submissions per student or the number of unique raters. CONCLUSIONS: The results of this study demonstrate that preceptors in the family medicine clerkship rate QR code-linked feedback as a high usability platform. Additionally, this platform resulted in faster form completion than paper or online forms. An overarching finding of this study is that feedback forms must be portable and easily accessible. Potential implementation barriers and the social norm for providing feedback in this manner need to be considered.

Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia.

Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but approximately 50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.

AFM of self-assembled lambda DNA-histone networks.

Atomic force microscopy (AFM) was used to investigate the self-assembly behavior of λ-DNA and histones at varying histone:DNA ratios. Without histones and at the lowest histone:DNA ratio (less than one histone per 1000 base pairs of DNA), the DNA appeared as individual (uncomplexed), double-stranded DNA molecules. At increasing histone concentrations (one histone per 500, 250 and 167 base pairs of DNA), the DNA molecules started to form extensive polygonal networks of mostly pentagons and hexagons. The observed networks might be one of the naturally occurring, stable DNA-histone structures. The condensing effects of the divalent cations Mg(2+) and Ca(2+) on the DNA-histone complexes were also investigated. The networks persisted at high Mg(2+) concentration (20mM) and the highest histone concentration. At high Ca(2+) concentration and the highest histone concentration, the polygonal network disappeared and, instead, individual, tightly condensed aggregates were formed.

Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST). This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.