An improved method of supercharged transposed latissimus dorsi flap with the skin paddle for the management of a complicated lumbosacral defect

OBJECTIVE: Treatment of nonhealing wounds of lower back often poses a powerful challenge. We present one of the first report of treatment of a lumbosacral defect with a supercharged latissimus dorsi flap with the skin paddle. CASE REPORT: We report a case of a 59 yearold man with myeloma of the sacral spine who underwent radiotherapy and chemotherapy and subsequently, laminectomies and placement of hardware for ongoing paresis and spine instability. Then, he developed an open wound and osteomyelitis of the spine with culture positive tuberculous granulomas. After multiple surgical debridement, he presented to our service and was treated with a single stage debridement followed by the performance of a latissimus dorsi musculocutaneous flap based on paraspinal perforators and supercharged. RESULTS: This solution, allowed for augmentation of blood flow to the muscle with the inferior gluteal artery, provided coverage of the defect resistant to the pressure, and simplified post-operative management of the patient. CONCLUSIONS: Alternative treatment options, including free tissue transfer, posed difficulties in finding suitable recipient vessels near the defect, in inserting the flap so as to restore its original length without compromising blood flow, and in postoperative care of the patient. Treatment of a lumbosacral defect with a supercharged latissimus dorsi flap with the skin paddle may represent a milestone procedure for complicated lower spine wounds

Stabilization of fault slip by fluid injection in the laboratory and in situ

Faults can slip seismically or aseismically depending on their hydromechanical properties, which can be measured in the laboratory. Here, we demonstrate that fault slip induced by fluid injection in a natural fault at the decametric scale is quantitatively consistent with fault slip and frictional properties measured in the laboratory. The increase in fluid pressure first induces accelerating aseismic creep and fault opening. As the fluid pressure increases further, friction becomes mainly rate strengthening, favoring aseismic slip. Our study reveals how coupling between fault slip and fluid flow promotes stable fault creep during fluid injection. Seismicity is most probably triggered indirectly by the fluid injection due to loading of nonpressurized fault patches by aseismic creep

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

Objective: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. Method: A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. Results: 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs -0.7 (-1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ -0.4 (-0.9 to -0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (-0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (-0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. Conclusion: LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women

An improved method of supercharged transposed latissimus dorsi flap with the skin paddle for the management of a complicated lumbosacral defect

OBJECTIVE: Treatment of non-healing wounds of lower back often poses a powerful challenge. We present one of the first report of treatment of a lumbosacral defect with a supercharged latissimus dorsi flap with the skin paddle. CASE REPORT: We report a case of a 59 year-old man with myeloma of the sacral spine who underwent radiotherapy and chemotherapy and subsequently, laminectomies and placement of hardware for ongoing paresis and spine instability. Then, he developed an open wound and osteomyelitis of the spine with culture positive tuberculous granulomas. After multiple surgical debridement, he presented to our service and was treated with a single stage debridement followed by the performance of a latissimus dorsi musculocutaneous flap based on paraspinal perforators and supercharged. RESULTS: This solution, allowed for augmentation of blood flow to the muscle with the inferior gluteal artery, provided coverage of the defect resistant to the pressure, and simplified post-operative management of the patient. CONCLUSIONS: Alternative treatment options, including free tissue transfer, posed difficulties in finding suitable recipient vessels near the defect, in inserting the flap so as to restore its original length without compromising blood flow, and in postoperative care of the patient. Treatment of a lumbosacral defect with a supercharged latissimus dorsi flap with the skin paddle may represent a milestone procedure for complicated lower spine wounds

S100B‑p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin‑4 and metalloproteinase‑2 inhibition in C6 glioma cells

S100 calcium‑binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B‑p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5 diphenyltetrazolium bromide‑formazan assay. Significant dose‑dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 μM (58.5±5%; P<0.05), 0.5 μM (40.6±7%; P<0.01) and 5 μM (13±4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 μM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl‑2 (‑60%, P<0.001; ‑80.13%, P<0.001; ‑95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 μM pentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, P<0.05; 1244±94.3%, P<0.01; and 2244±111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase‑2 (42±2.3%, P<0.05; 71±2.5%, P<0.01; and 95.8±3.3%, P<0.001, respectively) and aquaporin 4 (38±2.5%, P<0.05; 69±2.6%, P<0.01; and 88±3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 μM pentamidine compared with untreated cells (88±4.2%, P<0.05; 64±2%, P<0.01; and 42±3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B‑p53 inhibitors may represent a novel approach for the treatment of glioma

Excited States of Proton-bound DNA/RNA Base Homo-dimers: Pyrimidines

We are presenting the electronic photo fragment spectra of the protonated pyrimidine DNA bases homo-dimers. Only the thymine dimer exhibits a well structured vibrational progression, while protonated monomer shows broad vibrational bands. This shows that proton bonding can block some non radiative processes present in the monomer.Comment: We acknowledge the use of the computing facility cluster GMPCS of the LUMAT federation (FR LUMAT 2764

Complex mosaic structural variations in human fetal brains

Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200-400 mosaic SNVs per cell in three human fetal brains (15 to 21 weeks post-conception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones and we timed its origin to ~14 weeks post-conception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extra-chromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs, and present in ~10% neurons, SVs in developing human brain affect a comparable number of bases in the genome (~6,200 vs ~4,000 bps), implying that they may have similar functional consequences

Familial breast cancer: characteristics and outcome of BRCA 1–2 positive and negative cases

BACKGROUND: The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1–2 mutation are poorly known. METHODS: From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. RESULTS: BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40% – p = 0.002 at univariate analysis, not significant at multivariate analysis) and negative estrogen receptors (43% vs 29%). Treatment was not different in the two groups. In the 86 BRCA-WT patients, the first event was a local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and distant metastases in 16 (19%). In the 39 BRCA positive patients, the corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in event free survival, with a median of 180 months in both groups of patients. At 20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA-WT, but this difference was not statistically significant. CONCLUSION: Although BRCA positive patients have more frequently negative prognostic factors, their prognosis appears to be equal to or better than in patients with BRCA-WT

Treatment of established postoperative nausea and vomiting: a quantitative systematic review

BACKGROUND: The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood. METHODS: Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000) for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. RESULTS: In seven trials (1,267 patients), 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809) had placebo controls. Dolasetron 12.5–100 mg, granisetron 0.1–3 mg, tropisetron 0.5–5 mg, and ondansetron 1–8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%–30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK(1) antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. CONCLUSIONS: Of 100 vomiting surgical patients receiving a 5-HT(3) receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed

A 10 year follow-up study after Roux-Elmslie-Trillat treatment for cases of patellar instability

<p>Abstract</p> <p>Background</p> <p>A retrospective study concerning patients presenting with patella instability, treated using a Roux-Elmslie-Trillat reconstruction operation and followed up for 10 years following surgery, is presented.</p> <p>Methods</p> <p>Pre-operative and follow-up radiographic evaluation included the weight-bearing anteroposterior and merchant views. Evaluation was carried out using the Insall-Salvati index, sulcus and congruence angle. The Roux-Elmslie-Trillat reconstruction operation was performed on 18 patients. The clinical evaluation at follow-up was performed using the Knee-Society-Score (KSS) and Tegner-Score.</p> <p>Results</p> <p>Subjective results of the operation were classed as excellent or good in 16 of the 18 patients ten years after surgery; persistent instability of the patella was recorded in only one of the 18 patients. The majority of patients returned to the same level of sporting activity after surgery as they had participated in before injury.</p> <p>Conclusions</p> <p>The Roux-Elmslie-Trillat procedure could be recommended in cases presenting with an increased q-angle, trochlea dysplasia or failed soft tissue surgery. In the present study the majority of patients report a return to previous sporting activity ten years after surgery.</p