PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment.

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a "surveillant" of telomere replication, which orchestrates protein dynamics at proceeding replication fork.

Multiscale analysis of bamboo deformation mechanisms following NaOH treatment using X-ray and correlative microscopy.

For hundreds of years, bamboo has been employed for a variety of applications ranging from load-bearing structures to textiles. Thanks to its hierarchical structure that is functionally graded and naturally optimised, bamboo displays a variation in properties across its stem that ensures exceptional flexural performance. Often, alkaline solutions are employed for the treatment of bamboo in order to alter its natural elastic behaviour and make it suitable for particular applications. In this work we study the effect of NaOH solutions of five different concentrations (up to 25%) on the elastic properties of bamboo. By exploiting the capabilities of modern experimental techniques such as in situ synchrotron X-ray scattering and Digital Image Correlation, we present detailed analysis of the deformation mechanisms taking place in the main constituents of bamboo, i.e. fibres and matrix (Parenchyma). The principal achievement of this study is the elucidation of the deformation mechanisms at the fibre scale, where the relative sliding of fibrils plays a crucial role in the property modification of the whole bamboo stem. Furthermore, we shed light on the parenchyma toughness variation as a consequence of alkali treatments. STATEMENT OF SIGNIFICANCE: Alkaline solutions are often employed for the treatment of bamboo in order to alter its natural elastic behaviour. In this work we study the effect of alkaline solutions on the elastic properties of bamboo. Using state of the art experimental techniques allowed shedding light on the deformation mechanisms occurring in the bamboo main constituents, i.e. fibres and matrix (parenchyma cells). Enhancement of fibre stiffness was experienced when up to 20% NaOH solution was employed, while for higher concentration a decay was observed. This effect was imputed to the modification of adhesion between fibrils induced by disruption of ligand elements (e.g. lignin). Modification of the matrix toughness was also experienced, that indicated an improved resistance to cracking when the concentration of NaOH is 25%, while reduction of toughness was revealed for lower concentrations.

Strain softening of nano-scale fuzzy interfaces causes Mullins effect in thermoplastic polyurethane.

The strain-induced softening of thermoplastic polyurethane elastomers (TPUs), known as the Mullins effect, arises from their multi-phase structure. We used the combination of small- and wide- angle X-ray scattering (SAXS/WAXS) during in situ repeated tensile loading to elucidate the relationship between molecular architecture, nano-strain, and macro-scale mechanical properties. Insights obtained from our analysis highlight the importance of the 'fuzzy interface' between the hard and soft regions that governs the structure evolution at nanometre length scales and leads to macroscopic stiffness reduction. We propose a hierarchical Eshelby inclusion model of phase interaction mediated by the 'fuzzy interface' that accommodates the nano-strain gradient between hard and soft regions and undergoes tension-induced softening, causing the Mullins effect that becomes apparent in TPUs even at moderate tensile strains.

The modern, hybrid total hip arthroplasty for primary osteoarthritis at the Hospital for Special Surgery.

We describe our technique and rationale using hybrid fixation for primary total hip arthroplasty (THA) at the Hospital for Special Surgery. Modern uncemented acetabular components have few screw holes, or no holes, polished inner surfaces, improved locking mechanisms, and maximised thickness and shell-liner conformity. Uncemented sockets can be combined with highly cross-linked polyethylene liners, which have demonstrated very low wear and osteolysis rates after ten to 15 years of implantation. The results of cement fixation with a smooth or polished surface finished stem have been excellent, virtually eliminating complications seen with cementless fixation like peri-operative femoral fractures and thigh pain. Although mid-term results of modern cementless stems are encouraging, the long-term data do not show reduced revision rates for cementless stems compared with cemented smooth stems. In this paper we review the conduct of a hybrid THA, with emphasis on pre-operative planning, surgical technique, hypotensive epidural anaesthesia, and intra-operative physiology.

Thromboembolic disease in hip replacement surgery.

Total hip replacement surgery carries the risk of thromboembolic complications, which could be fatal. Over the last three decades however, the risk has decreased considerably thanks to progress made in the understanding of the physiopathogenetic mechanism of thromboembolic disease and perioperative prophylaxis. It is the purpose of this study to discuss the main medical and surgical preventive measures that must be carried out before, during and immediately after surgery. The old concept of deciding thromboembolic prophylaxis after surgery is now obsolete.

5-Methoxypsoralen increases the plasma melatonin levels in humans.

The aim of this study was to evaluate the acute effects of 5-methoxypsoralen (5-MOP) on the melatonin secretion in humans. Eleven normal volunteers were investigated before (drug-free) and after 6-day periods of treatment with oral 5-MOP, first administered daily at 9 A.M. and after a 1-week free interval administered daily at 9 P.M. Under nyctohemeral conditions, the plasma melatonin levels were evaluated over a 24-h period in each session by hourly blood samples and radioimmunoassay. The sensitivity of the retina to light was also evaluated by means of electroretinography performed at 11 A.M. before and after a morning administration of 5-MOP. Plasma levels of melatonin were significantly increased from the second hour after 5-MOP administration. The hourly mean levels were significantly higher after 5-MOP administration compared to baseline values. This increased secretion was more pronounced after evening than after morning administration. Also, 5-MOP increases the sensitivity of the retina to light under photopic conditions and in the early stages of the dark adaptation period, as observed under scotopic conditions.

5-Methoxypsoralen as a specific stimulating agent of melatonin secretion in humans.

The endocrine effects of the linear furocoumarin, 5-methoxypsoralen (Bergapten), were investigated in 11 normal adults according to a cross-over design with 2 conditions: a 1-week trial with 5-methoxypsoralen (5MOP) administered daily (40 mg/orally) at 0900 h, and after a 1-week period of washout, a similar 1-week trial with daily administrations of 5MOP at 2100 h. The subjects were living under normal nychtohemeral conditions. The plasma levels of melatonin, cortisol, TSH, PRL, and GH were evaluated by hourly blood samples over 24-h periods on the preceding day and on the last day of each condition. Our main finding is that 5MOP specifically stimulates melatonin secretion in humans, with a pronounced effect when administered during the dark phase of the day (at 2100 h). The other endocrine rhythms were unaffected by 5MOP administration. Melatonin has been shown to interact with the regulation of the human circadian system; this specific stimulation may, therefore, be of great interest in disorders associated with abnormalities of circadian rhythms.

Abnormal melatonin response to 5-methoxypsoralen in dementia.

The authors investigated the melatonin response to 5-methoxypsoralen in 39 healthy adult and elderly subjects and in 13 demented, 13 depressed, and 13 schizophrenic inpatients. Subjects' plasma melatonin levels were evaluated before they took single, oral 40-mg doses of 5-methoxypsoralen and 3 hours afterward. The preliminary results indicate that the melatonin response of the pineal gland to 5-methoxypsoralen is reduced in demented patients compared to that in healthy elderly subjects. Depressed and schizophrenic patients had a normal melatonin response to the drug. This finding suggests that the pineal gland may be functionally impaired in dementia but not in depression.

Twenty-four-hour profiles of body temperature and plasma TSH in bipolar patients during depression and during remission and in normal control subjects.

The 24-hour patterns of body temperature and plasma thyrotropin (TSH) were measured in eight bipolar patients in both depressed and recovered (after 3 weeks of treatment) states and in eight normal control subjects. Clear circadian patterns were detected for both temperature and TSH. Nocturnal body temperature was increased and the nocturnal surge of TSH was blunted during depression; these abnormalities were corrected after recovery. The inverse relationship between changes in body temperature and TSH levels at night suggests that changes in thermoregulation may be responsible for the neuroendocrine disturbance and may play a role in the pathophysiology of depression.

Group B streptococcal arthritis in adults.

Group B streptococcal arthritis in adults is uncommon. This report describes seven cases seen at these institutions over the past five years and reviews the previous 17 documented cases. Of seven adults, three were diabetics, three had prosthetic hips, and one had undergone splenectomy. Six had undergone no prior dental, genitourinary, or gastrointestinal procedures. The most common clinical presentation was fever and acute joint pain. Five patients had monoarticular arthritis; two had multiple joint involvement. Underlying joint abnormalities included osteoarthritis (two), prosthetic hip (three), and neuropathic joint (one). Bacteremia was documented in three and suspected in the remaining four patients, often without a primary source. Therapy included parenteral antibiotics, usually penicillin G, and drainage of the involved joint. Two of three patients with prosthetic implants required Girdlestone procedures; the third was apparently cured. The three diabetic patients died, one with resolution of group B streptococcal arthritis. The seventh patient was cured. Group B streptococcal arthritis is a serious infection in adults with diabetes and late prosthetic hip infections.

Antidepressant effect of 5-methoxypsoralen: a preliminary report.

5-Methoxypsoralen (5 MOP) administered daily (40 mg at 9 p.m.) was compared with placebo in the treatment of severe depression. The clinical response was evaluated using the Hamilton Depression Rating Scale after 1 week of treatment. Our preliminary data indicate that patients receiving 5 MOP improved significantly after 1 week, whereas patients treated with placebo did not. The stimulating effect of 5 MOP on the melatonin secretion may be involved in this clinical effect.

Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report.

Five patients with endogenous depression were asked to participate in a phase-advance procedure consisting in advancing by 5 h the time schedule of the major external synchronizers such as light/dark, sleep/wake, meal time and social activity cycles. Clinical and biological parameters were observed throughout this 2-week process which followed one night of partial sleep deprivation. All patients improved with partial sleep deprivation and four of the five showed continuing remission during the phase-advance process. The antidepressant effects of the phase-advance process are discussed in light of different chronobiological models for depression.

Seasonality of suicides: environmental, sociological and biological covariations.

The monthly rates of completed suicides in France from 1978 until 1982 were analyzed. The seasonal variations of environmental (daylight and sunlight durations, mean temperature, geomagnetism), sociological (unemployment, deaths of all causes, birth and conception rates), and biological (melatonin, cortisol and serotonin circannual rhythms) factors were compared to the seasonal patterns of suicides. A clear seasonal variation (with peaks in May and September) in suicidal behavior was detected. These patterns tended to differ as a function of age (bimodal in young, unimodal in old people). The component analysis clearly pointed out that seasonal patterns of suicides may be considered as the sum of two components, unimodal and bimodal. Almost similar covariations were found between the main seasonal (unimodal) component of suicides and environmental (daylight duration and mean monthly temperature) or sociological factors whereas the secondary component was more correlated to variations in environmental factors and, to some extent, to biological parameters.

Electrocoagulation as primary therapy for rectal carcinoma.

The survival of forty-seven patients with cancer of the rectum treated by electrocoagulation is compared with thirty-seven patients treated by abdominoperineal resection. The one to ten year survival for the electrocoagulationgroup was 48 per cent and the one to eight year survival for the abdominoperineal resection group was 46 per cent. We believe that electrocoagulation when selectively applied has a place in the management of cancer of the rectum.

Five year survival in patients with carcinoma of the rectum treated by electrocoagulation.

Sixty-eight patients with rectal cancer treated by electrocoagulation are reviewed. All were followed up for a minimum of 5 years. The survival rate in patients with small exophytic cancers is greater than 70 percent. However, the recurrence rate after electrocoagulation is 40 percent. Electrocoagulation offers an alternative for the primary treatment of rectal cancer, particularly in older patients with small lesions.

The problem of infection in total prosthetic arthroplasty of the hip.

In summary, deep wound infection carries a special and disastrous significance for the patient with a total joint prosthesis. Such patients seem to be at greater than usual risk of infection, and special precautionary measures to prevent it are not only justified but imperative. These include careful preoperative preparation; special attention to rigid and exacting operative techniques for control of potential exogenous contaminants; sensible preoperative, intraoperative, and postoperative antibiotic prophylaxis for control of potential endogenous cantaminants; and continued supervision of the patient throughout the postoperative years so as to prevent potential metastatic infection from other primary sources. Pre-existing and active infections of the hip constitute contraindications to total prosthetic arthroplasty, but these rules may be suspended in certain special situations provided that the patient is willing to cooperate with the arduous and prolonged program of treatment, and fully understands the special risks involved.

Thromboembolism following total hip-replacement arthroplasty. The efficicy of dextran-aspirin and dextran-warfarin in prophylaxis.

The efficacy of two antithrombotic regimens, combined dextran and aspirin and combined dextran and warfarin, was analyzed by comparing the incidence of thromboembolism following total hip replacement in two groups of similar patients. Of the 427 who received dextran and aspirin, 7 per cent had thromboembolic complications, including one case of fatal pulmonary embolus and one case of recurrent emboli that required vena caval ligation, and 15 per cent had wound-healing complications. Of the 197 patients who received dextran and warfarin, 5 per cent had thromboembolism and 24 per cent had wound healing complications. Although both prophylactic regimens seemed effective, dextran and aspirin appeared less effective in reducing thromboembolic complications than dextran and warfarin, but there were fewer wound complications in that group. One-fourth of the patients on dextran-warfarin were not adequately anticoagulated despite close supervision. In forty-five patients with a history of thromboembolism who were excluded from the study and analyzed separately, warfarin alone and the two described regimens were equally ineffective in preventing thromboembolism, and the incidence of thromboembolic complications was high. Dextran-aspirin and dextran-warfarin appear to be satisfactory and relatively simple methods of thromboembolic prophylaxis.

Bilateral total hip-replacement arthroplasty in one stage.

We reviewed 122 single-stage bilateral total hip replacements as compared with two other regimens: bilateral total hip replacement performed in stages during the same hospitalization and during separate hospitalizations. When compared with the single procedures, the duration of surgery in the one-stage procedure was not quite doubled while the blood loss was increased by about one-third and the length of stay by about one week. However, the total length of stay in the hospital was reduced by about one-half in comparison with single-admission two-stage replacements and the incidence of local and systemic complications was similar for all three groups, as were the clinical and roentgenographic results. There was one death in the single-stage group due to massive fat embolus.

Effect of aspirin on heterotopic ossification after total hip arthroplasty in men who have osteoarthrosis.

The severity of heterotopic ossification was determined from the radiographs of eighty-three men in whom osteoarthrosis had been treated with a primary total hip arthroplasty with cement. The medical records of these patients were then reviewed, with the reviewer having no knowledge of the radiographic findings. A similar operative approach and technique had been used in all patients. There was no association between the amount of intraoperative loss of blood or the duration of the operation and the severity of formation of heterotopic bone. The over-all rate of occurrence of heterotopic ossification was 72 per cent. Of the fifty-eight patients who had received aspirin throughout their course in the hospital, two (3 per cent) had severe ectopic ossification (grade III or IV8). In contrast, twelve (48 per cent) of the twenty-five patients who had received no aspirin or in whom aspirin had been discontinued so that anticoagulation could be begun had severe heterotopic ossification. The difference in the severity of the ossification between the two groups is significant (p less than 0.0001).

The CAD hip arthroplasty. Five to ten-year follow-up.

One hundred and fourteen total hip arthroplasties in 100 patients were performed using the CAD (computer-assisted design) prosthesis at The Hospital for Special Surgery between 1975 and 1977. Sixty-one of these patients (seventy-four hips) have been followed both clinically and radiographically for a minimum of five years (average, 7.1 years). While no hip required revision before five years, seven hips were revised between six and ten years postoperatively. Ten hips had an excellent result; forty-eight, good; eight, fair; and one, poor. Radiographic analysis revealed narrowing of the cortex of the bone medially at the region of the proximal part of the stem in the hips that were operated on as compared with the contralateral side that was not operated on. Nine hips (12 per cent) had one to two-millimeter radiolucent lines at the femoral bone-cement interface, and in five the lines were progressive. Fourteen hips (19 per cent) had radiolucent lines at the femoral bone-cement interface with a maximum width of 0.5 millimeter. Thirty-four (42 per cent) had more than three millimeters of resorption of the calcar or superomedial cyst formation. Survivorship analysis of the prosthesis predicted a 77 per cent survival rate at nine years. None of the prosthetic stems fractured despite the fact that the population was young, active, heavy, and predominantly male. The incidence of calcar resorption, however, was higher than in other studies. Thus, while the revision rate compared favorably with that of similar studies using other stem designs, compromise of the bone stock of the proximal end of the femur may be a significant disadvantage of this type of prosthesis.