Increased WDR spontaneous activity and receptive field size in rats following a neuropathic or inflammatory injury: implications for mechanical sensitivity

Spontaneous activity and receptive field size for spinal wide dynamic range (WDR) neurons were measured and related to the mechanical allodynia in both neuropathic (L5-L6 ligation, 14 days post-injury) and complete Freund's adjuvant-inflamed rats (CFA, 2 days post-injury). The size of the WDR receptive field located on the hindpaw expanded significantly (p<0.01) following both modes of injury, with no difference between CFA and neuropathic animals. Likewise, the spontaneous firing of WDR neurons was significantly elevated following both the CFA (4.4+/-0.6 spikes/s, p<0.01) and neuropathic (3.2+/-0.3 spikes/s, p<0.05) injuries compared to naive (2.1+/-0.2 spikes/s) and sham-neuropathic (1.9+/-0.3 spikes/s) rats. Furthermore, the spontaneous WDR activity recorded from CFA rats was also significantly greater (p<0.05) than neuropathic rats. Mechanical allodynia, as measured by application of a von Frey hair stimulus, was observed from both CFA and neuropathic rats, however, the degree of sensitivity was significantly greater (p<0.01) for the CFA animals. These data suggest that the differences in mechanical sensitivity between CFA and neuropathic rats may be related to their respective changes in WDR spontaneous activity, but not to the changes in receptive field size, and is further demonstration of the importance of spontaneous WDR activity in determining mechanical sensitivity following injury.     

Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure.

Graft failure is associated with a high mortality rate. To date, regimens invoked for second transplants have resulted in inconsistent engraftment with high transplant-related mortality (TRM). We here report 16 consecutive patients, aged 4-59 years, who received second HSCT (HSCT-2) at a median of 45 days following primary or secondary failure of an initial unmodified (N = 3) or T cell-depleted (TCD) (N = 13) HSCT (HSCT-1). HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). All patients experienced 1 or more infectious complications between HSCT-1 and HSCT-2, and 10 patients had active infections at the time of HSCT-2. Cytoreduction regimens used for HSCT-2 included fludarabine (Flu) in combination with cyclophosphamide (CTX) (N = 9), or thiotepa (Thio) (N = 5). In addition, 1 patient received Flu alone and 1 patient Thio combined with CTX. Antithymocyte globulin (ATG) (N = 11) or Alemtuzumab (N = 3) was added pretransplant to prevent rejection. For HSCT-2, donors included HLA-matched (N = 3) or mismatched (N = 8) related, or matched (N = 2) or mismatched (N = 3) unrelated donors. The primary graft donor was used in 6 of 16 cases. The grafts administered were unmodified peripheral blood stem cell transplantation (PBSCT) (N = 5) or bone marrow transplantation (BMT) (N = 3), TCD PBSCT (N = 8). All patients achieved engraftment at a median of 12 days and evaluable patients achieved complete donor chimerism. Six patients are alive with a median follow-up of 49 months, including 4/9 conditioned with Flu/CTX. In this series, outcome was statistically superior for younger patients (相似文献   

Estimate of Burden and Direct Healthcare Cost of Infectious Waterborne Disease in the United States

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million–12.0 million), results in 601,000 ED visits (95% CrI 364,000–866,000), 118,000 hospitalizations (95% CrI 86,800–150,000), and 6,630 deaths (95% CrI 4,520–8,870) and incurring US $3.33 billion (95% CrI 1.37 billion–8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.     

Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS) training for emergency medicine and general surgery residents

BackgroundSuccessful trauma resuscitation relies on multi-disciplinary collaboration. In most academic programs, general surgery (GS) and emergency medicine (EM) residents rarely train together before functioning as a team.MethodsIn our Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS), EM and GS residents completed manikin-based trauma scenarios and were evaluated on resuscitation and communication skills. Residents were surveyed on confidence surrounding training objectives.ResultsResidents showed improved confidence running trauma scenarios in multi-disciplinary teams. Residents received lower communication scores from same-discipline vs cross-discipline faculty. EM residents scored higher in evaluation and planning domains; GS residents scored higher in action processes; groups scored equally in team management. Strong correlation existed between team leader communication and resuscitative skill completion.ConclusionMD-TEAMS demonstrated correlation between communication and resuscitation checklist item completion and communication differences by resident specialty. In the future, we plan to evaluate training-related resident behavior changes and specialty-specific communication differences by residents.     

The Validity of Women's Reports of Family Planning Service Quality in Cambodia and Kenya

Population‐based indicators of the coverage of key elements of high‐quality family planning services are tracked via household surveys with female respondents, yet little work has been done to establish their validity. We take advantage of existing data sets from Cambodia and Kenya to compare women's responses at exit interviews following a health facility visit against the observations of a trained third‐party observer during the visit. The results, which treat the observations as the reference standard, show that indicators that measure contraceptive methods received are accurately reported while indicators of whether the woman received her preferred method and whether information was “discussed” or “explained” during counseling are less reliably reported. Studies designed explicitly to assess the validity of family planning questions in household surveys, especially questions in large survey programs critical for monitoring demographic trends and programmatic coverage, are needed.     

Septation of the respiratory and digestive tracts in human embryos: Crucial role of the tracheoesophageal sulcus

Esophageal atresia and tracheoesophageal fistula, common malformations of the respiratory and digestive tracts, are of unsettled pathogenesis. Part of the difficulty in understanding these abnormalities arises from the uncertainties about the normal developmental processes in the region. This study examined the development and fate of the tracheoesophageal septum. Normal human embryos from the Carnegie Embryological Collection and fetuses from the Hopkins Pathology Collection were examined, and reconstructions of selected specimens were made from photomicrographs of serial histologic sections. The results show that the lung bud appears in Carnegie stage 12, rapidly enlarges, and bend caudally, thereby producing a sulcus between the foregut and the respiratory system on its caudal aspect. The cranial aspect of this tracheoesophageal sulcus remains fixed at the levels of the first cervical vertebra throughout subsequent embryonic and fetal development. At the same time the trachea and esophagus elongate to bring those parts of the respiratory and digestive systems into their definitive anatomic positions. Examination of the tracheoesophageal sulcus shows that its growth-limiting properties may be explained by its catenoidal configuration. Catenoidal, or saddle-shape, sulci have been shown to have similar regional growth-limiting properties in the embryonic heart. These regions contrast with outwardly convex regions in both the developing heart and lung where growth of the tissues occurs. The observations made here suggest that the origin of the tracheoesophageal malformations must be sought in a configurational abnormality in the area of the developing lung bud in Carnegie stage 12. © 1994 Wiley-Liss, Inc.     

SOX5: Lamb–Shaffer syndrome—A case series further expanding the phenotypic spectrum

To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant.     

Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor andα 2 adrenoceptor blockade on naloxone-induced antinociception

Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature=51.5 ± 0.5°C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or ₂ adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5–10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT₁ or 5-HT₃ receptors by methiothepin or MDL 72222, respectively, or by the ₂ adrenoceptor blocker idazoxan. None of the 5-HT or ₂ adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT₂ receptors in the antinociception induced by opioid receptor blockade is discussed.     

Body Dysmorphic Disorder and Depression: Theoretical Considerations and Treatment Strategies

Body dysmorphic disorder (BDD), also known as dysmorphophobia, consists of a distressing and impairing preoccupation with an imagined or slight defect in appearance. BDD is an underrecognized and relatively common disorder that is associated with high rates of occupational and social impairment, hospitalization, and suicide attempts. BDD is unlikely to simply be a symptom of depression, although it often coexists with depression and may be related to depression. It is important to recognize BDD in depressed patients, because missing the diagnosis can result in refractory BDD and depressive symptoms. Available data indicate that BDD may not respond to all treatments for depression and may instead respond preferentially to serotonin-reuptake inhibitors. In addition, lengthier treatment trials than those required for depression may be needed to successfully treat BDD and comorbid depression. It can be difficult and challenging to diagnose BDD in depressed patients because the symptoms are often concealed due to embarrassment and shame. This paper discusses the relationship between BDD and depression and discusses practical strategies for recognizing and treating BDD and depressive symptoms in patients with depression.