High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome.

OBJECTIVE: Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS. DESIGN: A retrospective study. SETTING: An outpatient clinic for musculoskeletal disorders. SUBJECTS: Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected. METHODS: Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size. RESULTS: In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females. CONCLUSIONS: In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.

Phenolic Hydrogen Transfer by Molecular Oxygen and Hydroperoxyl Radicals. Insights into the Mechanism of the Anthraquinone Process.

Hydrogen atom transfer (HAT) by 3O2 and HO2• from arenols (ArOH), aryloxyls (ArO•), their tautomers (ArH), and auxiliary compounds has been investigated by means of CBS-QB3 computations. With 3O2, excellent linear correlations have been found between the activation enthalpy and the overall reaction enthalpy. Different pathways have been discerned for HATs involving OH or CH moieties. The results for ArOH + HO2• → ArO• + H2O2 neither afford a linear correlation nor agree with the experiment. The precise mechanism for the liquid-phase autoxidation of anthrahydroquinone (AnH2Q) appears to be not fully understood. A kinetic analysis shows that the HAT by chain-carrying HO2• occurs with a high rate constant of ≥6 × 108 M-1 s-1 (toluene). The second propagation step pertains to a diffusion-controlled HAT by 3O2 from the 10-OH-9-anthroxyl radical. Oxanthrone (AnOH) is a more stable tautomer of AnH2Q with a ratio of 13 (298 K) in non-hydrogen-bonding (HB) solvents, but the reactivity toward 3O2/HO2• is much lower. Combination of the computed free energies and Abrahams' HB donating (α2H) and accepting (ß2H) parameters has afforded an α2H(HO2•) of 0.86 and an α2H(H2O2) of 0.50.

Symptomatic Tarlov cysts are often overlooked: ten reasons why-a narrative review.

PURPOSE: Tarlov cysts (TCs) are dilations of nerve roots arising from pathologically increased hydrostatic pressure (HP) in the spinal canal. There is much controversy regarding whether these cysts are a rare source of pain or often produce symptoms. The aim of this review was to identify the reasons that symptomatic TCs (STCs) are easily overlooked. METHODS: The literature was searched for data regarding pathogenesis and symptomatology. RESULTS: TCs may be overlooked for the following reasons: (1) STCs are considered clinically irrelevant findings; (2) it is assumed that it is clinically difficult to ascertain that TCs are the cause of pain; (3) MRI or electromyography studies only focus on the L1 to S1 nerves; (4) TCs are usually not reported by radiologists; (5) degenerative alterations of the lumbosacral spine are almost always identified as the cause of a patient's pain; (6) it is not generally known that small TCs can be symptomatic; (7) examinations and treatments usually focus on the cysts as an underlying mechanism; however, essentially, increased HP is the main underlying mechanism for producing symptoms. Consequently, STCs may relapse after surgery; (8) bladder, bowel and sphincter dysfunction are not inquired about during history taking. (9) Unexplained pain is often attributed to depression, whereas depression is more likely the consequence of debilitating neuropathic pain. (10) The recognition of STCs is subject to gender bias, confirmation bias and cognitive dissonance and unconscious bias in publishing. CONCLUSION: There are several reasons STCs are underdiagnosed, mostly due to persistent misconceptions and biases. These slides can be retrieved under Electronic Supplementary Material.

Comment on "trans-1,2-Disiloxybenzocyclobutene, an adequate partner for the auto-oxidation: EPR/spin trapping and theoretical studies" by J. Drujon et al., Phys. Chem. Chem. Phys., 2014, 16, 7513.

Despite the claim of the contrary, (i) the facile formation of a ring-opened cyclic peroxide from reaction of a 1,2-disubstituted benzocyclobutene with molecular oxygen has been reported before, and (ii) the analysis of the mechanistic steps of this process is incomplete, as only the symmetry-allowed conrotatory ring-opening of the benzocyclobutene has been considered. The probable involvement of biradical intermediates/biradicaloid transition states in a formally symmetry-forbidden reaction sequence has not been taken into account.

Nanometer-grooved topography stimulates trabecular bone regeneration around a concave implant in a rat femoral medulla model.

In the present study, a method was developed to reproduce two nanogrooved patterns (groove width/ridge width/depth: 150/150/50 nm and 200/800/70 nm) into cylindrical epoxy resin implants, which were subsequently coated with 20 nm of titanium. Also, implants with a conventional surface roughness (Rq=1.6 µm) were produced. After cytocompatibility analysis of the produced surfaces, implants were installed into the femoral condyle of rats for 4 and 8 weeks. The histomorphometrical analysis of bone volume in a 100 µm wide zone close to the implant surface showed that only for the 200/800 grooves the amount of bone increased significantly between 4 and 8 weeks of implantation. In addition, at the late time point only implants with the 200/800 pattern revealed a significantly higher bone volume compared to the rough controls. In conclusion, the 200/800 grooved pattern can positively influence bone volume adjacent to the implant surface, and should be evaluated and optimized in further (pre-)clinical studies.

Electromyographic Abnormalities Associated with Symptomatic Sacral Tarlov Cysts.

Tarlov or perineural cysts (TC) are commonly overlooked as a cause of sacral and ischial pain, and urogenital and bowel problems. TC can be seen on MRI, but are often considered asymptomatic. This is especially true for smaller cysts. Moreover, there are only few diagnostic characteristics that can be used to confirm that the cysts are the cause of the symptoms. As a consequence, a lot of controversy remains regarding the clinical importance of TC. Because of this underdiagnosed condition, patients often suffer for several years from unrecognized chronic neuropathic pain and neurological conditions. In this article, case reports of three patients with giant and smaller symptomatic sacral cysts are presented, in which electromyographic testing was performed to demonstrate nerve damage. We suggest that electromyography of the sacral nerve roots can be a reasonable tool for the diagnosis of symptomatic TC, as well as for the differentiation from other pathological entities causing sacral and ischial pain. Moreover, using electromyography it was also documented that smaller cysts of < 1 cm can cause nerve damage. Therefore incidence of symptomatic TC may be higher than initially thought.

Tautomerization of Some Methylacenes and the Role of Reverse Radical Disproportionation.

The thermokinetics for the tautomerization of a series of methylenedihydroacenes to the corresponding methylacenes (toluene to 6-methylpentacene) have been investigated by means of CBS-QB3 calculations. Only for 6-methylpentacene does the methylenedihydro form predominate at room temperature. The obtained equilibrium ratios are consistent with various theoretical methods, but the agreement with the scarce experimental data is only qualitative. The noncatalyzed thermal tautomerization of the methylenedihydroacene in an inert solvent may proceed by means of a reverse radical disproportionation reaction (RRD) as the rate-determining step. The benzylic BDE(C-H)s and the hydrogen atom affinities (HA) of the tautomers have been used to calculate the reaction enthalpy, ΔRRDH. It appears that the Ea,RRD is substantially higher than ΔRRDH. This implies that the opposite reaction (and the tautomer forming step), a radical-radical disproportionation (RD), is an activated process. This is an often ignored or overlooked kinetic feature. The consequence is that although the RRD reaction may be kinetically feasible at elevated temperatures, the products are not the tautomers but rather dimers stemming from radical-radical recombination reactions, with p-isotoluene as a clear exception. It is further shown that the RRD self-reaction of phenalene is too slow at 298 K, despite claims to the contrary.

Reduced Surface Recombination in Extended-Perimeter LEDs toward Electroluminescent Cooling.

III-V semiconductor light-emitting diodes (LEDs) are a promising candidate for demonstrating electroluminescent cooling. However, exceptionally high internal quantum efficiency designs are paramount to achieving this goal. A significant loss mechanism preventing unity internal quantum efficiency in GaAs-based devices is nonradiative surface recombination at the perimeter sidewall. To address this issue, an unconventional LED design is presented, in which the distance from the central current injection area to the device's perimeter is extended while maintaining a constant front contact grid size. This approach effectively moves the perimeter beyond the lateral spread of current at an operating current density of 101-102 A/cm2. In p-i-n GaAs/InGaP double heterojunction LEDs fabricated with varying sizes and perimeter extensions, a 19% relative increase in external quantum efficiency is achieved by extending the perimeter-to-contact distance from 25 to 250 µm for a front contact grid size of 450 × 450 µm2. Utilizing an in-house developed Photon Dynamics model, the corresponding relative increase in internal quantum efficiency is estimated to be 5%. These results are ascribed to a significant reduction in perimeter recombination due to a lower perimeter-to-surface area (P/A) ratio. However, in contrast to lowering the P/A ratio by increasing the front contact grid size of LEDs, the present method enables these improvements without affecting the required maximum current density in the microscopic active LED area under the front contact grid. These findings aid in the advancement of electroluminescent cooling in LEDs and could prove useful in other dedicated semiconductor devices where perimeter recombination is limiting.

Anthrone and related hydroxyarenes: tautomerization and hydrogen bonding.

The keto-enolization of hydroxyl-substituted naphthols and 9-anthrols has been investigated by means of CBS-QB3 calculations. An excellent agreement between experiment and theory is found for the energetics for the anthrone (5) ⇌ anthrol (6) equilibrium, with an enthalpy of tautomerization, Δ(t)H, of 3.8 kcal mol(-1). In contrast, 1-naphthol is the preferred tautomer with a Δ(t)H = -9.0 kcal mol(-1). Substitution of the hydrogens at the adjacent carbons by hydroxyl groups leads to the formation of strong intramolecular hydrogen bonds within a six-membered ring in the enones and the enols. Due to the difference in the intramolecular hydrogen bond enthalpy, Δ(HB)H(intra), the equilibrium shifts further to the enone. Thus, for 1,8-dihydroxy-anthrone (anthralin, dithranol) Δ(t)H increases to 12.7 kcal mol(-1) with an enol/enone ratio of 10(-10). The solvent effect on the 5 ⇌ 6 equilibrium has been quantified by considering the formation of intermolecular hydrogen bond(s), leading to an acidity parameter α2(H) for anthrol of 0.42. It is shown that the hydrogen bond donating ability of bulk methanol is greatly attenuated through the formation of cyclic oligomers. The benzylic and phenolic bond dissociation enthalpies for anthrone up to anthralin suggest some antioxidant potency but the precise (radical) mechanism of action remains uncertain.

The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure.

The etiopathogenesis of fibromyalgia (FM) and chronic fatigue syndrome (CFS) is not yet elucidated. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is reflected in the hormonal disturbances found in FM and CFS. Some study groups have introduced a novel hypothesis that moderate or intermittent intracranial hypertension may be involved in the etiopathogenesis of FM and CFS. In these conditions, hormonal disturbances may be caused by the mechanical effect of increased cerebrospinal fluid pressure, which hampers blood flow in the pituitary gland. Severe intracranial pressure may compress the pituitary gland, resulting in primary empty sella (ES), potentially leading to pituitary hormone deficiencies. The aim of this narrative review was to explore whether similar hormonal changes and symptoms exist between primary ES and FM or CFS and to link them to cerebrospinal fluid pressure dysregulation. A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy). Furthermore, challenge tests of the pituitary gland showed similar abnormalities in all three conditions: blunted adrenocorticotropic hormone, cortisol, growth hormone, luteinizing hormone, and thyroid stimulating hormone responses and an increased prolactin response. The findings of this narrative review provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure is involved in the pathogenesis of FM and CFS and should stimulate further research into the etiopathogenesis of these conditions.

Electrodiagnostic Abnormalities Associated with Fibromyalgia.

PURPOSE: Increasing evidence suggests that fibromyalgia most likely represents a neurological dysfunction. We previously hypothesized that at least some fibromyalgia cases may be caused by irritation of nerve root fibers and sensory neurons due to moderately increased cerebrospinal pressure. Because of the rostro-caudal hydrostatic pressure gradient, neurogenic abnormalities are expected to be most pronounced in sacral nerve roots. The purpose was to review electrodiagnostic tests of patients with fibromyalgia. METHODS: A retrospective review of electrodiagnostic test results, including the lumbar and sacral nerve root myotomes of patients diagnosed with fibromyalgia according to the 1990 criteria of the American College of Rheumatology was done. RESULTS: All 17 patients were female. Sural nerve responses could not be elicited in 12% and S1-Hoffmann reflex latencies were increased in 41%. In 12% of the patients, fibular motor nerve distal latency and conduction velocity were outside normal limits. Needle-EMG revealed neurogenic motor unit potentials in 0% of L2, 6% of L3, 29% of L4, 71% of L5, 47% of S1, 94% of S2, and 76% of S3-S4 myotomes. S3-S4 nerve-supplied anal reflexes were delayed in 94%. CONCLUSION: This is the first time that electrodiagnostic data of both lumbar and sacral nerve root myotomes in fibromyalgia patients are presented. All patients showed neurogenic abnormalities that were more pronounced in the sacral than in the lumbar myotomes with a rather patchy distribution pattern. We propose that, in addition to skin punch biopsies to assess small fiber neuropathy, assessment of the anal reflex may be a useful part of the diagnostic pathway in patients with fibromyalgia.

Intramolecular and intermolecular hydrogen bond formation by some ortho-substituted phenols: some surprising results from an experimental and theoretical investigation.

The effects produced by addition of various concentrations of the strong hydrogen bond (HB) acceptor, dimethyl sulfoxide (DMSO), on the OH fundamental stretching region of the IR spectra of several o-methoxy, o-nitro, and o-carbonyl phenols in CCl(4) are reported. In most of these phenols the intramolecular HB is not broken by the DMSO. Instead, the DMSO acts as a HB acceptor to the intramolecular HB forming a bifurcated intra/intermolecular HB. For o-methoxyphenols the bifurcated HBs are observed as new IR bands at much lower wavenumbers (Deltanu(OH) approximately -300 cm(-1)) than the band due to their intramolecular HB. The formation of bifurcated HBs and the large frequency shift of their OH bands in o-methoxyphenols are well reproduced by theoretical modeling. In contrast to the o-methoxyphenols DMSO has little effect (other than causing some broadening) on the intramolecular HB OH bands of o-nitro and o-carbonyl phenols, with the single exception of 2,4-dinitrophenol. In this case, but not for 2,4-diformylphenol, the intramolecular HB OH band decreases as the DMSO concentration increases and a new absorption grows in at lower wavenumbers, indicating that DMSO can break this intra-HB and form an inter-HB, a result well reproduced by theory. Although DMSO has little effect on the O-H stretching band of 2-nitrophenol, theory indicates extensive formation (90%) of bifurcated HBs with OH stretching bands at slightly higher wavenumbers (Deltanu(OH) approximately +20 cm(-1)) than that for the intramolecular HB OH group and 10% of a "simple" intermolecular HB in which the intramolecular HB has been broken. Theory also indicates that, with DMSO, 2-formylphenol also forms a bifurcated HB (Deltanu(OH) approximately +150 cm(-1)), whereas 2,4-diformylphenol forms both intermolecular HBs (Deltanu(OH) approximately -130 cm(-1)) and bifurcated HBs (Deltanu(OH) approximately +165 cm(-1)). The IR spectrum of 2-methoxymethylphenol shows that although an intramolecular HB conformer is dominant there is a small percentage of a "free" OH, non-HB conformer (2.1% in CCl(4), 1.5% in cyclohexane). These results are quantitatively reproduced by theory. We conclude that theory can provide important insights into the formation and structure of inter, intra, and bifurcated HBs, and into their OH stretching frequencies, that are not always revealed by IR studies alone.

Hydrocephalus associated with multiple Tarlov cysts.

Tarlov cysts (TCs) consist of dilated nerve root sheaths filled with cerebrospinal fluid (CSF) and are most frequently found in the sacrum. It is estimated that 25% of detected TCs cause chronic pain and intestinal and urogenital symptoms due to compression of the sacral nerve root fibers inside the TC. Unfortunately, symptomatic TCs are frequently overlooked. It is assumed that TCs result from pathologically increased hydrostatic pressure (HP) in the dural sac that forces CSF into the nerve root sheaths. We hypothesize that in patients with TCs, increased spinal hydrostatic pressure is always associated with increased intracranial pressure. This hypothesis of increased cerebrospinal pressure might explain why patients with sacral TCs frequently report distant symptoms, such as headaches and pain in the neck and arms. In this paper, we describe a case report that provides evidence for this hypothesis. A 30-year-old man presented for the first time in our clinic complaining of lower back, leg, thoracic, neck, and arm pain; headaches; and bladder, bowel, and sphincter symptoms. He was born prematurely and suffered cerebral intraventricular bleeding followed by progressive hydrocephalus. Progression was stabilized with acetazolamide and lumbar punctures. At 19 years of age, his head circumference had further increased and he reported back pain and headaches. Fundoscopy showed no papilledema, and lumbar puncture for CSF evacuation improved the headaches and back pain. The former medical team chose not to insert a ventriculo-external shunt. Brain magnetic resonance imaging (MRI) showed significant dilation of all the ventricles. No CSF flow obstruction between the ventricles was observed. Surprisingly, MRI of the lumbar and sacral spine showed multiple large TCs. This case report indicates that hydrocephalus with a patent aqueduct may be associated with TCs because the increased intracranial pressure is transferred to the spinal canal. While increased intracranial pressure causes dilation of the ventricles, the associated increased spinal pressure may cause dilation of multiple spinal nerve root sheaths to form TCs. Furthermore, while the increased volume of the ventricles gradually compresses the neurons and axons of the brain against the bony skull, simultaneously, the increased pressure inside the nerve sheaths may also gradually compress the neurons and axons located inside the dorsal root ganglia and spinal nerves, resulting in neuropathic pain, sensory abnormalities, and neurogenic bladder and bowel symptoms. Hydrocephalus patients reporting neuropathic pain should be screened for the presence of TCs.

Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) adnexectomy for benign pathology compared with laparoscopic excision (NOTABLE): a protocol for a randomised controlled trial.

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) uses natural orifices to access the cavities of the human body to perform surgical interventions. NOTES limits the magnitude of surgical trauma and potentially reduces postoperative pain. Our group published a protocol on a randomised study comparing transvaginal NOTES (vNOTES) versus laparoscopy for hysterectomy (HALON). We simultaneously designed a similar randomised controlled trial (RCT) comparing vNOTES with laparoscopy for adnexectomy. To the best of our knowledge, this is the first RCT comparing vNOTES with laparoscopy for adnexal surgery. METHODS AND ANALYSIS: The methodology of the Notes Adnexectomy for Benign Indication versus Laparoscopic Excision (NOTABLE) study is similar to that of the HALON trial. Women aged 18-70 years with an indication for benign adnexal surgery will be eligible. We will use stratification according to adnexal size. Entrants will be randomised to the laparoscopic treatment (control) or vNOTES (intervention). Participants will be evaluated on days 0-7 and at 3 and 6 months. The primary outcome will be the proportion of women successfully treated by removing an adnexa by the allocated technique without conversion. We will collect the following data (secondary outcomes): proportion of women hospitalised on the day of surgery, postoperative pain scores measured two times per day from day 1 to 7, total dosage of pain killers used from day 1 to 7, hospital readmission during the first 6 weeks, dyspareunia and sexual well-being at baseline, 3 and 6 months using a validated questionnaire (Short Sexual Functioning Scale), health-related quality of life at baseline, 3 and 6 months after surgery using a validated questionnaire (EQ-5D-3L), duration of surgical intervention, infection or other surgical complications and direct costs up to 6 weeks following surgery. For the primary outcome measure, a one-sided 95% CI of the difference in the proportions of women with a successful removal of the uterus by the randomised technique will be estimated. Non-inferiority will be concluded when 15% lies above the upper limit of this 95% CI. ETHICS AND DISSEMINATION: The study was approved on 1 December 2015 by the EthicsCommitteeof the Imelda Hospital (registration no: 689), Bonheiden, Belgium. We aim to present the final results of the NOTABLE trial in peer-reviewed journals and at scientific meetings within 4 years after the start of the recruitment. TRIAL REGISTRATION NUMBER: NCT02630329.

Postoperative outcomes and quality of life following hysterectomy by natural orifice transluminal endoscopic surgery (NOTES) compared to laparoscopy in women with a non-prolapsed uterus and benign gynaecological disease: a systematic review and meta-analysis.

OBJECTIVE: To critically appraise studies comparing benefits and harms in women with benign disease without prolapse undergoing hysterectomy by natural orifice transluminal endoscopic surgery (NOTES) versus laparoscopy. STUDY DESIGN: We followed the PRISMA guidelines. We searched MEDLINE, EMBASE and CENTRAL for randomised controlled trials (RCTs), controlled clinical trials (CCTs) and cohort studies comparing NOTES with laparoscopy assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH) in women bound to undergo removal of a non-prolapsed uterus for benign disease. Two authors searched and selected studies, extracted data and assessed the risk of bias independently. Any disagreement was resolved by discussion or arbitration. RESULTS: We did not find RCTs but retrieved two retrospective cohort studies comparing NOTES with LAVH. The study quality as assessed by the Newcastle-Ottawa scale was acceptable. Both studies reported no conversions. The operative time in women treated by NOTES was shorter compared to LAVH: the mean difference (MD) was -22.04min (95% CI -28.00min to -16.08min; 342 women; 2 studies). There were no differences for complications in women treated by NOTES compared to LAVH: the risk ratio (RR) was 0.57 (95% CI 0.17-1.91; 342 women; 2 studies). The length of stay was shorter in women treated by NOTES versus LAVH: the MD was -0.42days (95% CI -0.59days to -0.25days; 342 women; 2 studies). There were no differences for the median VAS scores at 12h between women treated by NOTES (median 2, range 0-6) or by LAVH (median 2, range 0-6) (48 women, 1 study). There were no differences in the median additional analgesic dose request in women treated by NOTES (median 0, range 0-6) or by LAVH (median 1, range 0-5) (48 women, 1 study). The hospital charges for treatment by NOTES were higher compared to LAVH: the mean difference was 137.00 € (95% CI 88.95-185.05 €; 294 women; 1 study). CONCLUSIONS: At the present NOTES should be considered as a technique under evaluation for use in gynaecological surgery. RCTs are needed to demonstrate its effectiveness.

HALON-hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery: a randomised controlled trial (study protocol).

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) uses natural body orifices to access the cavities of the human body to perform surgery. NOTES limits the magnitude of surgical trauma and has the potential to reduce postoperative pain. This is the first randomised study in women bound to undergo hysterectomy for benign gynaecological disease comparing NOTES with classical laparoscopy. METHODS AND ANALYSIS: All women aged 18-70 years, regardless of parity, consulting at our practice with an indication for hysterectomy due to benign gynaecological disease will be eligible. After stratification according to uterine size on clinical examination, participants will be randomised to be treated by laparoscopy or by transvaginal NOTES. Participants will be evaluated on day 0, days 1-7 and at 3 and 6 months. The following data will be collected: the proportion of women successfully treated by removing the uterus by the intended approach as randomised; the proportion of women admitted to the inpatient hospital; postoperative pain scores measured twice daily by the women from day 1 to 7; the total amount of analgesics used from day 1 to 7; readmission during the first 6 weeks; presence and intensity of dyspareunia and sexual well-being at baseline, 3 and 6 months (Short Sexual Functioning Scale (SSFS) scale); duration of surgery; postoperative infection or other surgical complications; direct and indirect costs incurred up to 6 weeks following surgery. The primary outcome will be the proportion of women successfully treated by the intended technique; all other outcomes are secondary. ETHICS AND DISSEMINATION: The study was approved on 1 December 2015 by the Ethics Committee of the Imelda Hospital, Bonheiden, Belgium. The first patient was randomised on 17 December 2015. The last participant randomised should be treated before 30 November 2017. The results will be presented in peer-reviewed journals and at scientific meetings within 4 years after starting recruitment. TRIAL REGISTRATION NUMBER: NCT02631837; Pre-results.

The Reactivity of o-Hydroxybenzyl Alcohol and Derivatives in Solution at Elevated Temperatures.

The reactivity of o-hydroxybenzyl alcohol (o-HBA, 1), as a model compound for lignin, has been studied in various solvents between 390 and 560 K. Both in polar and apolar solvents the benzylic cation is the reactive intermediate. In alcoholic solvents, the benzylic cation reacts with the solvent to give the corresponding ethers. Relative reaction rates have been determined for different alcohols; a factor of 14 is encountered between the most (methanol) and least (tert-butyl alcohol) reactive ones. The etherification is reversible, in contrast to the electrophilic aromatic substitution with phenol and anisole, for which k(PhOH) = 1 x 10(5) M(-)(1) s(-)(1) and k(anisole) = 1 x 10(4) M(-)(1) s(-)(1), at 424 K. In apolar hydroaromatic solvents, 7H-benz[de]anthracene, 9,10-dihydroanthracene, and 9,10-dihydrophenanthrene, the formation of o-cresol proceeds via hydride transfer from the solvent to the benzylic cation; rate constants at 555 K are 2 x 10(6), 5 x 10(4), and 5 x 10(3) M(-)(1) s(-)(1), respectively.