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A facile one-pot, two-step, reductive alkylation of amines with carboxylic acids has been achieved with BH 3 -NH 3 as an air- and moisture-stable reductant in the presence of TiF 4 . The catalyst is effective for both amidation and reduction steps, and the product amines are isolated in high yields as either the free amines, for those products containing an arylamine, or the borane-complexes. The free amine can be separated from these complexes using BF 3 -Et 2 O, followed by hydrolysis. The amide reduction has been demonstrated for primary, secondary, and tertiary amides, as well as lactams, and the reductive amination is applicable to a wide variety of aromatic and aliphatic acids as well as amines., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

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., (Copyright © 2022. Published by Elsevier Inc.)

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.

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., (© 2021 The American Association of Hip and Knee Surgeons. Published by Elsevier Inc.)

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., Competing Interests: The authors have no conflicts of interest to disclose.

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.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

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., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

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., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

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.

Introduction/background: Osteoporosis is a common disorder and is associated with an increased risk of bone fracture. Falls are a proximate cause of a high proportion of medical costs and mortality. Improving balance can reduce the risk of falls and improve health outcomes, especially for the at-risk population of people with osteoporosis and osteopenia. The FrameWorks TM exercise program is a formal, standardized, informational and interventional 10-month exercise program. The purpose of this study was to quantitatively assess the improvement in standing balance, functional reach, and overall confidence in balance after participating in the 10-month program., Methodology: This study is a prospectively designed study with a pre and post study measurement of balance metrics. Sixty-two female participants, 45 years of age or older and at increased risk for fragility fractures, completed the 10-month program as well the pre and post program testing. Confidence was measured with the Activities-specific Balance Confidence Scale, a self-reported survey. Balance was measured digitally by means of testing with a NeuroCom® Basic Balance Master® system. Measurements were made of the Limits of Stability (LOS) Test and Modified Clinical Test of Sensory Interaction on Balance (mCTSIB). Balance was clinically assessed with the Functional Reach Test (FRT)., Results: Participation in the 10 months FrameWorksTM program resulted in improvement in quantitative measures of balance (Composite Sway Velocity, -12%, p < 0.001; End point excursion, 17.1%, p < 0.000001). A clinical measure of balance, the Functional Reach Test, improved, (2.9 cm, p < 0.0001). Participation also resulted in improvement in balance confidence (9.4 %, p < 0.00001). A height increase was observed (0.6 cm, p < 0.000001)., Conclusions: The 10-month FrameWorks TM program improves balance and confidence in women at risk for fragility fractures. By improving balance and confidence, people are less likely to fall and therefore sustain fewer fractures and associated injuries., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Hospital acquired infections (HAIs) and the emergence of antibiotic resistant strains are major threats to human health. Copper is well known for its high antimicrobial efficacy, including the ability to kill superbugs and the notorious ESKAPE group of pathogens. We sought a material that maintains the antimicrobial efficacy of copper while minimizing the downsides - cost, appearance and metallic properties - that limit application. Here we describe a copper-glass ceramic powder as an additive for antimicrobial surfaces; its mechanism is based on the controlled release of copper (I) ions (Cu 1+ ) from cuprite nanocrystals that form in situ in the water labile phase of the biphasic glass ceramic. Latex paints containing copper-glass ceramic powder exhibit ≥99.9% reduction in S. aureus, P. aeruginosa, K. aerogenes and E. Coli colony counts when evaluated by the US EPA test method for efficacy of copper-alloy surfaces as sanitizer, approaching that of benchmark metallic copper.

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.

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.

In patients with portal hypertension, ectopic varices can develop at any site along the gastrointestinal tract outside the classically described gastroesophageal location. Like esophageal variceal hemorrhage, bleeding from ectopic varices can be life-threatening. Diagnosis and treatment of ectopic varices can be challenging; to date, no effective treatment algorithm has been described. A systematic teamwork approach to diagnosing and treatment of ectopic varices is required to successfully manage hemorrhage from ectopic varices., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Germline-expressed endogenous small interfering RNAs (endo-siRNAs) transmit multigenerational epigenetic information to ensure fertility in subsequent generations. In Caenorhabditis elegans, nuclear RNAi ensures robust inheritance of endo-siRNAs and deposition of repressive H3K9me3 marks at target loci. How target silencing is maintained in subsequent generations is poorly understood. We discovered that morc-1 is essential for transgenerational fertility and acts as an effector of endo-siRNAs. Unexpectedly, morc-1 is dispensable for siRNA inheritance but is required for target silencing and maintenance of siRNA-dependent chromatin organization. A forward genetic screen identified mutations in met-1, which encodes an H3K36 methyltransferase, as potent suppressors of morc-1(-) and nuclear RNAi mutant phenotypes. Further analysis of nuclear RNAi and morc-1(-) mutants revealed a progressive, met-1-dependent enrichment of H3K36me3, suggesting that robust fertility requires repression of MET-1 activity at nuclear RNAi targets. Without MORC-1 and nuclear RNAi, MET-1-mediated encroachment of euchromatin leads to detrimental decondensation of germline chromatin and germline mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Higher order chromosome structure and nuclear architecture can have profound effects on gene regulation. We analyzed how compartmentalizing the genome by tethering heterochromatic regions to the nuclear lamina affects dosage compensation in the nematode C. elegans. In this organism, the dosage compensation complex (DCC) binds both X chromosomes of hermaphrodites to repress transcription two-fold, thus balancing gene expression between XX hermaphrodites and XO males. X chromosome structure is disrupted by mutations in DCC subunits. Using X chromosome paint fluorescence microscopy, we found that X chromosome structure and subnuclear localization are also disrupted when the mechanisms that anchor heterochromatin to the nuclear lamina are defective. Strikingly, the heterochromatic left end of the X chromosome is less affected than the gene-rich middle region, which lacks heterochromatic anchors. These changes in X chromosome structure and subnuclear localization are accompanied by small, but significant levels of derepression of X-linked genes as measured by RNA-seq, without any observable defects in DCC localization and DCC-mediated changes in histone modifications. We propose a model in which heterochromatic tethers on the left arm of the X cooperate with the DCC to compact and peripherally relocate the X chromosomes, contributing to gene repression., Competing Interests: The authors have declared that no competing interests exist.

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.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

Objective: The objective of this study was to compare the short-term outcomes of robotic with conventional on-pump coronary artery bypass grafting (CABG)., Methods: The study population included 2091 consecutive patients who underwent either conventional or robotic CABG from January 2007 to March 2012. Preoperative, intraoperative, and 30-day postoperative variables were collected for each group. To compare the incidence of rapid recovery between conventional and robotic CABG, the surrogate variables of early discharge and discharge to home (vs rehabilitation or acute care facility) were evaluated. A multivariate logistic regression analysis was used., Results: One hundred fifty robotic and 1619 conventional CABG cases were analyzed. Multivariate logistic regression analysis demonstrated that robotic surgery was a strong predictor of lower 30-day complications [odds ratio (OR), 0.24; P = 0.005], short length of stay (OR, 3.31; P < 0.001), and decreased need for an acute care facility (OR, 0.55; P = 0.032). In the presence of complications (New York State Complication Composite), the robotic technique was not associated with a change in discharge status., Conclusions: In this retrospective review, robotic CABG was associated with a lower 30-day complication rate, a shorter length of stay, and a lower incidence of acute care facility discharge than conventional on-pump CABG. It may suggest a more rapid recovery to preoperative status after robotic surgery; however, only a randomized prospective study could confirm the advantages of a robotic approach.

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., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

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.

Dosage compensation (DC) equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, the dosage compensation complex (DCC) localizes to both X chromosomes in hermaphrodites and downregulates gene expression 2-fold. The DCC first localizes to hermaphrodite X chromosomes at the 30-cell stage, coincident with a developmental transition from plasticity to differentiation. To test whether DC onset is linked to loss of developmental plasticity, we established a timeline for the accumulation of DC-mediated chromatin features on X (depletion of histone H4 lysine 16 acetylation (H4K16ac) and enrichment of H4K20 monomethylation (H4K20me1)) in both wild type and developmentally delayed embryos. Surprisingly, we found that H4K16ac is depleted from the X even before the 30-cell stage in a DCC-independent manner. This depletion requires the activities of MES-2, MES-3, and MES-6 (a complex similar to the Polycomb Repressive Complex 2), and MES-4. By contrast, H4K20me1 becomes enriched on X chromosomes several cell cycles after DCC localization to the X, suggesting that it is a late mark in DC. MES-2 also promotes differentiation, and mes-2 mutant embryos exhibit prolonged developmental plasticity. Consistent with the hypothesis that the onset of DC is linked to differentiation, DCC localization and H4K20me1 accumulation on the X chromosomes are delayed in mes mutant hermaphrodite embryos. Furthermore, the onset of hermaphrodite-specific transcription of sdc-2 (which triggers DC) is delayed in mes-2 mutants. We propose that as embryonic blastomeres lose their developmental plasticity, hermaphrodite X chromosomes transition from a MES protein-regulated state to DCC-mediated repression., (© 2013 Published by Elsevier Inc.)

We used atomic force microscopy (AFM) to study the dose-dependent change in conformational and mechanical properties of DNA treated with PT-ACRAMTU ([PtCl(en)(ACRAMTU-S)](NO3)2, (en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea. PT-ACRAMTU is the parent drug of a family of non-classical platinum-based agents that show potent activity in non-small cell lung cancer in vitro and in vivo. Its acridine moiety intercalates between DNA bases, while the platinum group forms mono-adducts with DNA bases. AFM images show that PT-ACRAMTU causes some DNA looping and aggregation at drug-to-base pair ratio (r b) of 0.1 and higher. Very significant lengthening of the DNA was observed with increasing doses of PT-ACRAMTU, and reached saturation at an r b of 0.15. At r b of 0.1, lengthening was 0.6 nm per drug molecule, which is more than one fully stretched base pair stack can accommodate, indicating that ACRAMTU also disturbs the stacking of neighboring base pair stacks. Analysis of the AFM images based on the worm-like chain (WLC) model showed that PT-ACRAMTU did not change the flexibility of (non-aggregated) DNA, despite the extreme lengthening. The persistence length of untreated DNA and DNA treated with PT-ACRAMTU was in the range of 49-65 nm. Potential consequences of the perturbations caused by this agent for the recognition and processing of the DNA adducts it forms are discussed.

Dosage compensation equalizes X-linked gene expression between the sexes. This process is achieved in Caenorhabditis elegans by hermaphrodite-specific, dosage compensation complex (DCC)-mediated, 2-fold X chromosome downregulation. How the DCC downregulates gene expression is not known. By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. Depletion of H4K16ac also requires the conserved histone deacetylase SIR-2.1, while enrichment of H4K20me1 requires the activities of the histone methyltransferases SET-1 and SET-4. Our data suggest that the mechanism of dosage compensation in C. elegans involves redistribution of chromatin-modifying activities, leading to a depletion of H4K16ac and an enrichment of H4K20me1 on the X chromosomes. These results support conserved roles for histone H4 chromatin modification in worm dosage compensation analogous to those seen in flies, using similar elements and opposing strategies to achieve differential 2-fold changes in X-linked gene expression.

Context: Struma ovarii exhibiting malignant histology are uncommon, and an aggressive clinical course in the form of initial extraovarian spread or recurrence is even more exceptional for these tumors., Objective: To determine whether specific histologic features have predictive value in distinguishing clinically benign from clinically malignant struma ovarii., Design: Blinded analysis of 19 histologic characteristics of thyroid tumors was performed in 60 clinically benign and 26 clinically malignant struma ovarii cases, with long-term follow-up., Results: Except for lack of fibrosis and macrofollicular pattern, which were more common in biologically malignant tumors (P  =  .04 and P  =  .008, respectively), and trabecular pattern, which was associated with a benign clinical course (P  =  .03), none of the other histologic features was found to be correlated with clinical behavior. The presence of the following features was similar in the biologically benign and malignant tumors: papillae, pseudo-papillae, psammoma bodies, nuclear grooves, nuclear overlap, "orphan Annie" nuclei, nuclear pseudo-inclusions, prominent nucleoli, hypercellularity, colloid scalloping, eosinophilic cytoplasm, mitoses, vascular invasion, cytologic atypia, nuclear pleomorphism, and cell size and type. Trabecular pattern and absence of fibrosis were uncommon, and there was considerable overlap of macrofollicular pattern ratio between benign and malignant cases. Thus, their practical usefulness is uncertain., Conclusions: The clinical outcome of struma ovarii cannot be predicted based on the microscopic diagnosis of the thyroid tissue or on specific histologic features. The lack of correlation between morphology and outcome in proliferative and histologically malignant struma ovarii is striking, making the behavior of these tumors particularly unpredictable.

Dosage compensation ensures similar levels of X-linked gene products in males (XY or XO) and females (XX), despite their different numbers of X chromosomes. In mammals, flies, and worms, dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in one sex resulting in a change in gene expression from the affected X chromosome(s). In mammals and flies, dosage compensation is associated with specific histone posttranslational modifications and replacement with variant histones. Until now, no specific histone modifications or histone variants have been implicated in Caenorhabditis elegans dosage compensation. Taking a candidate approach, we have looked at specific histone modifications and variants on the C. elegans dosage compensated X chromosomes. Using RNAi-based assays, we show that reducing levels of the histone H2A variant, H2A.Z (HTZ-1 in C. elegans), leads to partial disruption of dosage compensation. By immunofluorescence, we have observed that HTZ-1 is under-represented on the dosage compensated X chromosomes, but not on the non-dosage compensated male X chromosome. We find that reduction of HTZ-1 levels by RNA interference (RNAi) and mutation results in only a very modest change in dosage compensation complex protein levels. However, in these animals, the X chromosome-specific localization of the complex is partially disrupted, with some nuclei displaying DCC localization beyond the X chromosome territory. We propose a model in which HTZ-1, directly or indirectly, serves to restrict the dosage compensation complex to the X chromosome by acting as or regulating the activity of an autosomal repellant., Competing Interests: The authors have declared that no competing interests exist.

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.

Purpose: Patients are frequently referred for resection of difficult colon polyps. Before colectomy the experienced surgeon has the option of repeating the colonoscopy to assess the polyp, tattoo the site, and potentially remove the polyp. The purpose of this study was to review our results with this approach., Methods: All new patients referred during a five-year period to an 11-physician colon and rectal surgical group with the diagnosis of colon polyp (CPT 211.3) that was not previously removed were retrospectively reviewed. Patients with rectal polyps, inflammatory bowel disease, previous cancer, or familial adenomatous polyposis were excluded. Patient demographics, details of the polyps, success of polypectomy, reasons for surgical resection, pathology, and complications were analyzed., Results: The study population consisted of 252 patients with a mean age of 65 years. Eighty patients underwent resection upon referral without a repeat colonoscopy. Upon resection, invasive cancers were found in 13 cases. A total of 172 patients underwent at least one repeat colonoscopy by the colorectal surgeon. Of this group, 101 patients had successful polypectomy, thus avoiding major colectomy. The remaining 71 patients had a subsequent colon resection after at least one repeat colonoscopy. In 26 cases the polyp site was tattooed for later localization. There were nine postpolypectomy hemorrhages treated nonoperatively and two perforations., Conclusions: Repeat colonoscopy by an experienced surgeon leads to complete removal and avoidance of major colectomy in 58 percent of these cases. Patients with large difficult polyps referred for resection should be considered for repeat colonoscopy before surgery.

Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) in perianal abscesses represents an underrecognized condition. It is unclear whether these abscesses differ in presentation or other characteristics from their non-MRSA counterparts., Methods: Patients diagnosed with perianal abscess, who underwent incision and drainage between January 2003 and September 2005, were identified retrospectively. Demographics, abscess characteristics (induration, erythema, abscess size, amount of purulence), presence of MRSA on culture, MRSA susceptibilities, and clinical course were collected., Results: A total of 104 patients (62.5 percent male; mean age, 42.7+/-13.7 years) were treated for perianal abscess. For the 69 patients cultured at drainage, MRSA was present in 34.8 percent (24/69) of cases (95 percent confidence interval, 24.6-46.6 percent). MRSA-positive patients did not significantly differ from MRSA-negative patients with respect to age, MRSA risk factors, duration of symptoms, white blood cell count at admission, or length of stay. Patients were more likely to be MRSA-positive if they possessed extensive induration (odds ratio, 6.52; P=0.003), extensive erythema (odds ratio, 5.75; P=0.003), or small amount of purulence (odds ratio, 9.72; P=0.006). Ischiorectal abscesses were significantly less likely to be MRSA-positive (odds ratio, 0.34; P=0.016). No patients with MRSA-positive abscesses developed fistulas. All MRSA isolates were resistant to beta-lactam antibiotics and had limited susceptibility to quinolones., Conclusions: The prevalence of MRSA in perianal abscesses has not been described previously and is higher in our group of patients than would be expected. MRSA-positive patients cannot be identified by risk factors alone. Antibiotic resistance spectra of MRSA vary from that of enteric bacteria typically seen in perianal abscesses. Therefore, it may be beneficial to culture all perianal abscesses with extensive induration and erythema or minimal purulence.

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.

Most endometrial carcinomas metastasize by invading myometrial lymphatics and spreading to regional lymph nodes. However, uterine serous carcinomas (USCs) metastasize frequently to peritoneal surfaces even when only minimally invasive. This study examines the methods of spread and the role of retrograde transtubal spread. Eighty-seven USCs treated by hysterectomy were identified. Primary peritoneal cases and cases with significant ovarian involvement were excluded. Eighty (92%) cases were pure serous, and the remainder had at least 25% serous histology. Fifty-four of 87 (62%) had extrauterine spread at hysterectomy, most commonly to peritoneal surfaces and sometimes to the pelvic lymph nodes. Twenty-six of 54 (48%) cases had no lymphatic/vascular (LV) invasion and 18/54 (33%) had no myometrial invasion. Eleven of these 54 (20%) patients with metastases lacked both myometrial and LV invasion, and the metastases involved the peritoneal surface more often than the lymph nodes (p<0.001). Three of the 11 cases had tumor clusters in the fallopian tube lumen. Another 13 cases also had clusters of tumor within the fallopian tube lumen, and all 16 cases had peritoneal spread (p<0.001). Extrauterine spread correlated highly with LV invasion (p<0.001) but not with the presence or depth of myometrial invasion. Retrograde transtubal implantation as well LV invasion are two important mechanisms by which USC spreads; all cases with tumor clusters in the fallopian tube lumen had peritoneal spread. This explains the phenomenon whereby patients with serous carcinomas confined to the endometrium and lacking LV invasion have widespread metastases to the peritoneum.

Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>>E2>EE2>DDD>>BisA>P4>E1>>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng/ml and was effective at this concentration in decreasing the sensitivities of the embryos to estradiol and estrogenic EDCs. The complete antagonist ICI 182,780 inhibited development at concentrations as low as 0.03 ng/ml but increased embryo sensitivity to estradiol and estrogenic EDCs. Estradiol and estrogenic EDCs all cause developmental toxicity in sea urchins through a TAM-sensitive but an ICI-insensitive mechanism. It remains to be demonstrated whether this mechanism involves an estrogen-responsive nuclear receptor (NR), a membrane receptor (NR or non-NR-related) or a completely different mechanism of toxicity. However, early embryo sensitivity and the differential response to SERM co-incubation further suggests more than one mode of EDC action in the developing sea urchin embryo.

Carcinosarcoma of the uterus has been poorly characterized on cervicovaginal (Pap) smears, and we examine whether they effectively screen for carcinosarcoma and whether an abnormal Pap smear result has any clinical importance. Twenty-five patients with histologically confirmed carcinosarcoma had a conventional Pap smear shortly before diagnosis. Eleven smears (44%) originally were read as abnormal (malignant or atypical), and 4 additional cases were read as abnormal on retrospective review (15/25 [60%]). All malignant elements were epithelial, and 2 cases (8%) had atypical spindle cells, but no diagnostic sarcoma. Cervical involvement was the only histologic parameter correlating with an abnormal Pap smear result (P = .04). Univariate analysis found stage III or IV disease was an adverse prognostic sign compared with stage I or II disease (mean survival, 8 vs 36 months, respectively; P = .001), and multivariate analysis indicated that an abnormal Pap smear result correlated with worse survival (P = .023). The conventional Pap smear is insensitive (60%) for detecting carcinosarcoma, but when the result is abnormal, the Pap is an important stage-independent adverse prognosticator.

Diverticular disease affects approximately two thirds of the population over the age of 70. While only a small fraction of these patients will develop diverticulitis, adequate radiological evaluation of diverticulitis and its complications is imperative in determining proper medical and surgical treatment. Clinical examination and laboratory tests alone have been found to be inaccurate in defining many aspects of the disease in up to 60% of cases. Over the past 30 years, contrast enema, computed tomography, and ultrasound have all been used extensively to diagnose the complications of diverticular disease. More recently, magnetic resonance imaging has been studied in patients with complicated diverticulitis. This article reviews the use of these different radiological modalities in diagnosing acute colonic diverticulitis and its complications.

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice., (Copyright 2004 Wiley-Liss, Inc.)

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.

Lobster claw muscle undergoes atrophy in correlation with increasing ecdysteroid (steroid molting hormone) titers during premolt. In vivo molecular chaperone (constitutive heat shock protein 70 [Hsc70], heat shock protein 70 [Hsp70], and Hsp90) and polyubiquitin messenger ribonucleic acid (mRNA) levels were examined in claw and abdominal muscles from individual premolt or intermolt lobsters. Polyubiquitin gene expression was assayed as a marker for muscle atrophy. Both Hsc70 and Hsp90 mRNA levels were significantly induced in premolt relative to intermolt lobster claw muscle, whereas Hsp70 mRNA levels were not. Hsp90 gene expression was significantly higher in premolt claw muscle when compared with abdominal muscle. Polyubiquitin mRNA levels were elevated in premolt when compared with intermolt claw muscle and significantly elevated relative to premolt abdominal muscle.

Bone marrow transplantation (BMT) has been shown to reverse or stabilize some manifestations of mucopolysaccharidosis I (Hurler syndrome). Idiopathic hyperammonemia (IHA) is a rare complication of solid organ and BMT that is characterized by elevated serum ammonia, normal liver enzymes, and abrupt onset of neurologic deterioration. We present the case of a 14-month-old male patient with Hurler syndrome who developed fatal IHA (ammonia = 2297 micromol/L) 31 days after a cord blood transplant. A complete autopsy was performed, with examination of both frozen and formalin-fixed paraffin-embedded (FFPE) tissues using a variety of special stains and electron microscopy. Hyperammonemia was documented by analysis of antemortem serum and postmortem cerebrospinal and vitreous fluid. Other causes of hyperammonemia, including Reye syndrome, were excluded. Histologic changes included centrilobular microvesicular steatosis of the liver and storage product present in multiple organs. The highly water-soluble mucopolysaccharide (MPS) storage product was best identified by colloidal iron staining of FFPE and unfixed air-dried fresh frozen liver sections. Alcian blue stains failed to convincingly demonstrate MPS in any of the liver sections. This is the first published report, to our knowledge, of IHA in a posttransplant patient younger than 18 years old or following transplantation for Hurler syndrome. Demonstration of the hepatic centrilobular microvesicular steatosis characteristic of IHA was complicated by the diffuse storage of MPS within the liver. MPS storage can be best detected in the liver using colloidal iron staining. Oil-red-O staining may be useful to document microvesicular steatosis in cases with a clinical history of hyperammonemia following solid organ or BMT. Determining if certain subsets of children are at increased risk for IHA requires further study.

The American lobster, Homarus americanus, encounters osmotic stress throughout its life cycle. To understand the molecular basis of osmotic stress responses in vivo, we used homologous cDNA probes to characterize the mRNA patterns of lobster HSP70 (=70-kDa heat-shock protein), HSP90 (=90-kDa heat-shock protein), and polyubiquitin during hypo- and hyper-osmotic stress in abdominal muscle and hepatopancreas (a digestive tissue) at 30, 60, and 120 min of osmotic stress. Hypo- and hyper-osmotic stress significantly increased the levels of the mRNAs encoding HSP70 and HSP90 in abdominal muscle. Hyper-osmotic stress increased HSP90 mRNA levels in hepatopancreas, but hypo-osmotic stress did not. Both abdominal muscle and hepatopancreas exhibited significant changes in polyubiquitin gene expression during osmotic stress. In abdominal muscle, polyubiquitin mRNA levels increased during both hypo- and hyper-osmotic stress. Hepatopancreas, however, showed a significant elevation in polyubiquitin mRNA only during hypo-osmotic stress.

Electrical current flow appears to be integral to the healing of collagen containing tissue, i.e., bone, cartilage, ligaments, tendons and skin. Accordingly, it is reasonable to hypothesize that externally applied electrical fields should be able to enhance healing, especially in conditions that have resisted more standard treatments. Nevertheless, applications of electrotherapeutics is challenging because the precise mechanism of action is unknown and, accordingly, there is an almost unlimited combination of stimulation parameters (e.g., type of waveform, voltage, current, phase, frequency, etc.) that can be applied to a treatment site. Presently, of the three major types of electrical stimulation, i.e., direct, and capacitive and inductive coupling, there is a growing trend toward utilization of the latter because of its efficacy and greater margin of safety. Although the mechanisms of action for enhanced healing of all three types remain elusive there is increasing evidence that electrical stimulation exerts its influence via effects at the cellular and/or molecular levels within the tissue. Utilization of electrotherapeutics has been most prevalent in bony injuries resistant to healing, but applications to severe lesions of skin and ligaments, and even to degenerative joint disease seems promising as cartilage has been shown to be more responsive than bone to applied electrical energy. We conclude that there is a clear trend toward greater orthopedic utilization of inductive stimulation and that, despite the lack of definitive guidelines relating specific parameters with specific conditions, electrotherapeutics appears to be a safe and often effective treatment for collagen containing tissues in many cases in which more standard therapies have failed.