Involvement of several transcriptional regulators in the differential expression of tfd genes in Cupriavidus necator JMP134

Cupriavidus necator JMP134 has been extensively studied because of its ability to degrade chloroaromatic compounds, including the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 3-chlorobenzoic acid (3-CB), which is achieved through the pJP4-encoded chlorocatechol degradation gene clusters: tfdCIDIEIFI and tfdDIICIIEIIFII. The present work describes a different tfd-genes expression profile depending on whether C. necator cells were induced with 2,4-D or 3-CB. By contrast, in vitro binding assays of the purified transcriptional activator TfdR showed similar binding to both tfd intergenic regions; these results were confirmed by in vivo studies of the expression of transcriptional lacZ fusions for these intergenic regions. Experiments aimed at investigating whether other pJP4 plasmid or chromosomal regulatory proteins could contribute to the differences in the response of both tfd promoters to induction by 2,4-D and 3-CB showed that the transcriptional regulators from the benzoate degradation pathway, CatR1 and CatR2, affected 3-CB- and 2,4-D-related growth capabilities. It was also determined that the ISJP4-interrupted protein TfdT decreased growth on 3-CB. In addition, an ORF with 34% amino acid identity to IclR-type transcriptional regulator members and located near the tfdII gene cluster module was shown to modulate the 2,4-D growth capability. Taken together, these results suggest that tfd transcriptional regulation in C. necator JMP134 is far more complex than previously thought and that it involves proteins from different transcriptional regulator families. [Int Microbiol 2009; 12(2):97-106

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Case Report Leiomyosarcoma of the Vagina: An Exceedingly Rare Diagnosis

Background. Primary leiomyosarcoma of the vagina is an exceedingly rare diagnosis. Current estimates are that this tumor could at most represent a mere 0.062% of malignant neoplasms in the female genital tract, although in actuality it is likely far less common. Case Presentation. A 70-year-old female gravida 3 para 2 with new onset palpable vaginal mass and pink vaginal discharge is diagnosed with primary leiomyosarcoma of the vagina. Chemotherapy is complicated by acute Lyme disease, and the patient requires a robotic-assisted total hysterectomy with bilateral salpingo-oophorectomy and partial vaginectomy. The patient remains without recurrence 18 months after surgery. Conclusion. Vaginal leiomyosarcoma is exceedingly rare with an aggressive course, high recurrence, and undetermined ideal treatment regimen. Its diagnosis can be delayed and its presentation varied. Information on this rare tumor type is predominantly through rare case reports with collective consensus on management lacking. The gynecologic oncologist must exercise prudence in individualizing treatment regimens for this rare yet aggressive malignancy

Leiomyosarcoma of the Vagina: An Exceedingly Rare Diagnosis

Background. Primary leiomyosarcoma of the vagina is an exceedingly rare diagnosis. Current estimates are that this tumor could at most represent a mere 0.062% of malignant neoplasms in the female genital tract, although in actuality it is likely far less common. Case Presentation. A 70-year-old female gravida 3 para 2 with new onset palpable vaginal mass and pink vaginal discharge is diagnosed with primary leiomyosarcoma of the vagina. Chemotherapy is complicated by acute Lyme disease, and the patient requires a robotic-assisted total hysterectomy with bilateral salpingo-oophorectomy and partial vaginectomy. The patient remains without recurrence 18 months after surgery. Conclusion. Vaginal leiomyosarcoma is exceedingly rare with an aggressive course, high recurrence, and undetermined ideal treatment regimen. Its diagnosis can be delayed and its presentation varied. Information on this rare tumor type is predominantly through rare case reports with collective consensus on management lacking. The gynecologic oncologist must exercise prudence in individualizing treatment regimens for this rare yet aggressive malignancy

A study using a canine hydrotherapy treadmill at five different conditions to kinematically assess range of motion of the thoracolumbar spine in dogs

Abstract Background Incline treadmill and underwater treadmill (UWTM) exercises are common canine rehabilitation modalities , which are often used in isolation in dogs recovering from spinal surgery. Early use of an incline during UWTM exercise may have the potential to improve rehabilitation outcomes in dogs, but, it is hypothesised that dorsoventral movement of the spine may be excessive meaning it is unsuitable in some circumstances. Objectives The purpose of this study was to identify changes in canine spinal kinematics in dogs when using a dry treadmill at different angles of incline compared to an underwater treadmill using the same inclines. Methods Eight dogs were encouraged to walk on a dry, horizontal, underwater treadmill as well as under the same conditions with both a 10% and 20% incline. This was then repeated at a 10% and 20% incline with the addition of water to hock level. Data were collected using reflective anatomical markers placed at the occipital protuberance, T1, T13, L3, L7 and sacral apex, captured by a high‐speed camera facing the lateral aspect of the treadmill. Dorsoventral motion of the spine as well as flexion, extension and range of motion (ROM) of T1, T13, L3 and L7 were recorded. Results We found significant differences in dorsoventral spinal ROM at T1, L3 and L7, but no significant differences in T13 ROM. No significant differences were found in flexion and extension of any of the joints assessed when comparing dry conditions to the use of water (P>0.05). Conclusions The lack of significant differences in joint flexion and extension at T1, T13, L3 and L7 indicates the potential safe use of combining underwater treadmill and incline exercise in canine rehabilitation. However, a lack of uniformity in results makes distinguishing any patterns of significance difficult. More research is needed to establish the effects of these exercises in additional planes of motion before a treatment protocol can be established

Load to Failure of the Ankle Joint Complex After Fusion of the Subtalar and Talonavicular Joints: A Cadaveric Study.

Recent literature has proposed that restriction of joints in the rearfoot secondary to coalitions may lead to increased risk for severe ankle fracture after trauma. There is a paucity of literature regarding the rigidity of the ankle joint after arthrodesis of the subtalar and talonavicular joints. In this study, load-to-failure testing of cadaveric ankle joints with and without fusion of the subtalar and talonavicular joints was performed to determine if clinically relevant fracture patterns could be reproduced. Of the 3 fixation patterns studied, combined subtalar and talonavicular joint fusion resulted in a measurable increase in joint stiffness; however, this was not statistically significant. Clinical and radiographic examination postloading revealed that all tested ankle joints sustained a dislocation type injury rather than a specific bone fracture pattern. It was determined that a pure low-speed bending and compression model does not produce clinically relevant fracture patterns, and that higher energy mechanisms are required

Submission of the entire lymph node dissection for histologic examination in gynecologic-oncologic specimens. Clinical and pathologic relevance

BACKGROUND AND AIMS: Lymph node (LN) status in gynecologic malignancies plays an important role in patient staging, management, and prognosis. Therefore, an adequacy of LN harvest is crucial. The aim of this study is to determine whether the submission of the entire LN dissection for histologic examination will affect patients' outcome or clinical stage. We also evaluated the time required and cost-effectiveness for the laboratory. MATERIALS AND METHODS: A prospective study of 134 surgical cases from various gynecologic malignancies was conducted. The LN dissection specimen was performed using a conventional manual node dissection method with all the remaining fat being submitted in additional cassettes. One pathologist evaluated (1) the number and status of palpable LNs identified by the conventional method as well as the number of tissue cassettes and (2) the number, size, and status of the non-palpable LNs as well as the number of tissue cassettes. RESULTS: The palpable LNs ranged from 0 to 36 with average 14.8 LNs per case (Poisson 95% CI: 14.1-15.4). The additional non-palpable LNs ranged from 0 to 16 with an average of 3.1 (Poisson 95% CI: 2.8-3.4). In only one case, a 3-mm non-palpable LN with metastasis was identified; however, it did not affect tumor staging or patient management. CONCLUSION: The impact on patient outcome is minimal and it does not prove to be cost and time effective when submitting the entire LN dissection specimen in gynecologic malignancies. However, this method could be justified in selective cases in which the manual node dissection does not reveal an adequate number of LNs

A study using a canine hydrotherapy treadmill at five different conditions to kinematically assess range of motion of the thoracolumbar spine in dogs

Background: Incline treadmill and underwater treadmill (UWTM) exercises are common canine rehabilitation modalities , which are often used in isolation in dogs recovering from spinal surgery. Early use of an incline during UWTM exercise may have the potential to improve rehabilitation outcomes in dogs, but, it is hypothesised that dorsoventral movement of the spine may be excessive meaning it is unsuitable in some circumstances.Objectives: The purpose of this study was to identify changes in canine spinal kinematics in dogs when using a dry treadmill at different angles of incline compared to an underwater treadmill using the same inclines.MethodsEight dogs were encouraged to walk on a dry, horizontal, underwater treadmill as well as under the same conditions with both a 10% and 20% incline. This was then repeated at a 10% and 20% incline with the addition of water to hock level. Data were collected using reflective anatomical markers placed at the occipital protuberance, T1, T13, L3, L7 and sacral apex, captured by a high‐speed camera facing the lateral aspect of the treadmill. Dorsoventral motion of the spine as well as flexion, extension and range of motion (ROM) of T1, T13, L3 and L7 were recorded.ResultsWe found significant differences in dorsoventral spinal ROM at T1, L3 and L7, but no significant differences in T13 ROM. No significant differences were found in flexion and extension of any of the joints assessed when comparing dry conditions to the use of water (P>0.05).ConclusionsThe lack of significant differences in joint flexion and extension at T1, T13, L3 and L7 indicates the potential safe use of combining underwater treadmill and incline exercise in canine rehabilitation. However, a lack of uniformity in results makes distinguishing any patterns of significance difficult. More research is needed to establish the effects of these exercises in additional planes of motion before a treatment protocol can be established.</p

The Teenage Inventory of Social Skills: Reliability and Validity of the Spanish Translation

Peer relationships play a critical role in the development of social skills and personal feelings essential for personal growth and life-long adjustment (Hansen, Nangle, & Meyer, 1998), and are a key factor in the development of personal identity and independence from the family circle (Mayseless, Wiseman, & Hai, 1998). Children and adolescents who are popular or accepted by their peers receive more social reinforcement, which improves their adaptation, not only in social areas but also in personal and school ones (Inderbitzen, Walters, & Bukowski, 1997; La Greca & Lopez, 1998). Acceptance or popularity among peers is closely connected to prosocial behavior (Markiewicz, Doyle, & Brendgen, 2001). The Teenage Inventory of Social Skills (TISS; Inderbitzen, 1992) is the only self-report designed exclusively to reflect behaviors functionally related to peer acceptance in adolescence. The psychometric properties of the TISS have proved to be satisfactory in samples of adolescents in USA (Inderbitzen, 1992; Inderbitzen & Foster, 1992; Inderbitzen & Garbin, 1992), but they have not been examined among those who are Spanish-speaking. The aim of the present work was to determine the reliability and validity of the Spanish translation of the TISS