Structure-property relationships in renewable composites of poly(lactic acid) reinforced by low amounts of micro- and nano-kraft-lignin.

We investigate the direct and indirect effects of micro- and nano-kraft lignin, kL and NkL, respectively, at a quite low amount of 0.5 wt%, in poly(lactic acid) (PLA)-based composites. These renewable composites were prepared via two routes, either simple melt compounding or in situ reactive extrusion. The materials are selected and prepared using targeted methods in order to vary two variables, i.e., the size of kL and the synthetic method, while maintaining constant polymer chain lengths, L-/D-lactide isomer ratio and filler amounts. The direct/indirect effects were respectively investigated in the amorphous/semicrystalline state, as crystallinity plays in general a dominant role in polymers. The investigation involves structural, thermal and molecular mobility aspects. Non-extensive polymer-lignin interactions were recorded here, whereas the presence of the fillers led to both enhancements and suppressions of properties, e.g., glass transition, crystallization, melting temperatures, etc. The local and segmental molecular dynamics map of the said systems was constructed and is shown here for the first time, demonstrating both expected and unexpected trends. An interesting discrepancy between the trends in the calorimetric measurement against the dielectric Tg is revealed, providing indications for 'dynamical heterogeneities' in the composites as compared to neat PLA. The reactive extrusion as compared to compounding-based systems was found to exhibit stronger effects on crystallizability and mobility, most, probably due to the severe enhancement of the chains' diffusion. In general, the effects are more pronounced when employing nano-lignin compared to micro-lignin, which is the expected beneficial behaviour of nanocomposites vs. conventional composites. Interestingly, the variety of these effects can be easily manipulated by the proper selection of the preparation method and/or the thermal treatment under relatively mild conditions. The latter capability is actually desirable for processing and targeted applications and is proved here, once again, as an advantage of biobased polyesters such as PLA.

Segmental mobility in sustainable copolymers based on poly(lactic acid) blocks built onto poly(butylene succinate) in situ.

Two series of newly synthesized sustainable block copolymers based on poly(butylene succinate) (PBSu) and polylactide (PLA) were studied. The copolymers were synthesized by a ring-opening polymerization of PLA in the presence of two initial PBSu of low molar mass. We focused on the effects of the PBSu/PLA ratio (1/99 up to 15/85), chain length and initial PBSu length on the final thermal transitions in the copolymers with an emphasis on molecular mobility/dynamics and subsequently on crystallization. Both aspects are considered relevant to the final materials performance, as well as facilitation of polymer renewability. Calorimetry and dielectric spectroscopy were the main investigation tools. In the amorphous state (i.e., in which the direct effects of copolymer structure are assessable), the segmental mobility of neat PLA was significantly faster in the copolymers. Segmental mobility was monitored via the decrease in the calorimetric and dielectric (α relaxation) glass-transition temperatures, Tg and Tg,diel, respectively. The effect was systematic with an increase in the PBSu/PLA ratio, and was rationalized through the plasticizing role of PBSu (low-Tg component) and facilitated also by the simultaneous lowering of the chain length in the copolymers. Dielectric spectroscopy allowed evaluation of the dynamical fragility (cooperativity) of chains, which was strongly suppressed in the copolymers. This finding suggested an increase in free volume or a gradual increase of interchain distances. This phenomenon could favor the natural enzymatic degradation of the systems (compostability), which is limited in neat PLA. We recorded enhancement of nucleation and the crystalline fraction in the copolymers that was likely connected with faster chain diffusion. Further lowering of the Tg with the implementation of crystallization was noted (which seemed a controversial effect) but which indicated crystallization-induced phase separation.

Direct and indirect effects on molecular mobility in renewable polylactide-poly(propylene adipate) block copolymers as studied via dielectric spectroscopy and calorimetry.

In this work, we study a series of sustainable block copolymers based on polylactide, PLA, and poly(propylene adipate), PPAd, both polymers being prepared from renewable resources. Envisaging a wide range of future applications in the frame of a green and circular economy, e.g., packaging materials replacing conventional petrochemicals, the employment of PPAd aims at lowering the glass transition and melting temperatures of PLA and, finally, facilitation of the enzymatic degradation and compostability. The copolymers have been synthesized via ring opening polymerization of lactides in the presence of propylene adipate oligomers (5, 15 and 25%). The direct effects on the molecular mobility by the structure/composition are assessed in the amorphous state employing broadband dielectric spectroscopy (BDS) and calorimetry. BDS allowed the recording of local PLA and PPAd dynamics in all cases. The effects on local relaxations suggest favoring of interchain interactions, both PLA-PPAd and PPAd-PPAd. Regarding the more important segmental dynamics, the presence of PPAd leads to faster polymer chain diffusion, as monitored by the significant lowering of the dielectric and calorimetric glass transition temperature, Tg. This suggests the plasticizing role of PPAd on PLA (majority) in combination with the lowering of the average molar mass, Mn, in the copolymers from ∼75 to ∼30 kg mol-1, which is the actual scope for the synthesis of these materials. Interestingly, a strong suppression in fragility (chain cooperativity) is additionally recorded. In contrast to calorimetry and due to the high resolving power of BDS, for the higher PPAd fraction, the weak segmental relaxation of PPAd was additionally recorded. Overall, the recordings suggest a strong increase in free volume and two individual dynamic states, one for 0 and 5% PPAd and another for 15 and 25% PPAd. Within the latter, we gained indications for partial phase nano-separation of PPAd. Regarding indirect effects, these were followed via crystallization. Independent of the method of crystallization, namely, melt or cold, the presence of PPAd led to the systematic lowering of crystallization and melting temperatures and enthalpies. The effects reflect the decrease of crystalline nuclei, which is confirmed by optical microscopy as in the copolymers fewer although larger crystals are formed.

Revisiting Non-Conventional Crystallinity-Induced Effects on Molecular Mobility in Sustainable Diblock Copolymers of Poly(propylene adipate) and Polylactide.

This work deals with molecular mobility in renewable block copolymers based on polylactide (PLA) and poly(propylene adipate) (PPAd). In particular, we assess non-trivial effects on the mobility arising from the implementation of crystallization. Differential scanning calorimetry, polarized light microscopy and broadband dielectric spectroscopy were employed in combination for this study. The materials were subjected to various thermal treatments aiming at the manipulation of crystallization, namely, fast and slow cooling, isothermal melt- and cold-crystallization. Subsequently, we evaluated the changes recorded in the overall thermal behavior, semicrystalline morphology and molecular mobility (segmental and local). The molecular dynamics map for neat PPAd is presented here for the first time. Unexpectedly, the glass transition temperature, Tg, in the amorphous state drops upon crystallization by 8-50 K. The drop becomes stronger with the increase in the PPAd fraction. Compared to the amorphous state, crystallization leads to significantly faster segmental dynamics with severely suppressed cooperativity. For the PLA/PPAd copolymers, the effects are systematically stronger in the cold- as compared to the melt-crystallization, whereas the opposite happens for neat PLA. The local ßPLA relaxation of PLA was, interestingly, recorded to almost vanish upon crystallization. This suggests that the corresponding molecular groups (carbonyl) are strongly involved and immobilized within the semicrystalline regions. The overall results suggest the involvement of either spatial nanoconfinement imposed on the mobile chains within the inter-crystal amorphous areas and/or a crystallization-driven effect of nanophase separation. The latter phase separation seems to be at the origins of the significant discrepancy recorded between the calorimetric and dielectric recordings on Tg in the copolymers. Once again, compared to more conventional techniques such as calorimetry, dielectric spectroscopy was proved a powerful and quite sensitive tool in recording such effects as well as in providing indirect indications for the polymer chains' topology.

Poly(Lactic Acid) Composites with Lignin and Nanolignin Synthesized by In Situ Reactive Processing.

Poly(lactic acid) (PLA) composites with 0.5 wt% lignin or nanolignin were prepared with two different techniques: (a) conventional melt-mixing and (b) in situ Ring Opening Polymerization (ROP) by reactive processing. The ROP process was monitored by measuring the torque. The composites were synthesized rapidly using reactive processing that took under 20 min. When the catalyst amount was doubled, the reaction time was reduced to under 15 min. The dispersion, thermal transitions, mechanical properties, antioxidant activity, and optical properties of the resulting PLA-based composites were evaluated with SEM, DSC, nanoindentation, DPPH assay, and DRS spectroscopy. All reactive processing-prepared composites were characterized by means of SEM, GPC, and NMR to assess their morphology, molecular weight, and free lactide content. The benefits of the size reduction of lignin and the use of in situ ROP by reactive processing were demonstrated, as the reactive processing-produced nanolignin-containing composites had superior crystallization, mechanical, and antioxidant properties. These improvements were attributed to the participation of nanolignin in the ROP of lactide as a macroinitiator, resulting in PLA-grafted nanolignin particles that improved its dispersion.

Synthesis, Properties, and Enzymatic Hydrolysis of Poly(lactic acid)-co-Poly(propylene adipate) Block Copolymers Prepared by Reactive Extrusion.

Poly(lactic acid) (PLA) is a biobased polyester with ever-growing applications in the fields of packaging and medicine. Despite its popularity, it suffers from inherent brittleness, a very slow degradation rate and a high production cost. To tune the properties of PLA, block copolymers with poly(propylene adipate) (PPAd) prepolymer were prepared by polymerizing L-lactide and PPAd oligomers via reactive extrusion (REX) in a torque rheometer. The effect of reaction temperature and composition on the molecular weight, chemical structure, and physicochemical properties of the copolymers was studied. The introduction of PPAd successfully increased the elongation and the biodegradation rate of PLA. REX is an efficient and economical alternative method for the fast and continuous synthesis of PLA-based copolymers with tunable properties.

Pain chronification: what should a non-pain medicine specialist know?

OBJECTIVE: Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of "pain chronification". METHODS: This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification. RESULTS: Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: "Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification." CONCLUSIONS: Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.

Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms.

Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. DIAGNOSIS: Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. CONCLUSIONS: This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and anticonvulsants), supplemented by appropriate non-pharmacological measures such as exercise programs, manual therapies, behavioral therapies, interventional pain management and traction. Surgery may be appropriate in carefully selected patients.

A holistic approach to chronic pain management that involves all stakeholders: change is needed.

Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses', pharmacists' and physiotherapists' skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late. Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels - for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain. Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain - it is vital they continue.

Managing chronic pain in elderly patients requires a CHANGE of approach.

In many countries, the number of elderly people has increased rapidly in recent years and this is expected to continue; it has been predicted that almost a quarter of the population in the European Union will be over 65 years of age in 2035. Many elderly people suffer from chronic pain but it is regularly under-treated, partly because managing these patients is often complex. This paper outlines the extent of untreated pain in this population and the consequent reduction in quality of life, before articulating the reasons why it is poorly or inaccurately diagnosed. These include the patient's unwillingness to complain, atypical pain presentations, multiple morbidities and cognitive decline. Successful pain management depends upon accurate diagnosis, which is based upon a complete history and thorough physical examination, as well as an assessment of psychosocial functioning. Poor physician/patient communication can be improved by using standardized instruments to establish individual treatment targets and measure progress towards them. User-friendly observational instruments may be valuable for patients with dementia. In line with the widely accepted biopsychosocial model of pain, a multidisciplinary approach to pain management is recommended, with pharmacotherapy, psychological support, physical rehabilitation and interventional procedures available if required. Declining organ function and other physiological changes require lower initial doses of analgesics and less frequent dosing intervals, and the physician must be aware of all medications that the patient is taking, in order to avoid drug/drug interactions. Non-adherence to treatment is common, and various strategies can be employed to improve it; involving the elderly patient's caregivers and family, using medication systems such as pill-boxes, or even sending text messages. In the long term, the teaching of pain medicine needs to be improved--particularly in the use of opioids--both at undergraduate level and after qualification.

Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements.

Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.

The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment.

Chronic pain is currently under-diagnosed and under-treated, partly because doctors' training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain.

The chronic pain conundrum: should we CHANGE from relying on past history to assessing prognostic factors?

BACKGROUND: Despite limited empirical support, chronic pain has traditionally been defined mainly on the basis of its duration, which takes no account of the causative mechanisms or its clinical significance. SCOPE: For this commentary on current pain management practice, the CHANGE PAIN Advisory Board considered the evidence for adopting a prognostic definition of chronic pain. The rationale underlying this approach is to take psychological and behavioural factors into account, as well as the multidimensional nature of pain. Measures of pain intensity, interference with everyday activities, role disability, depression, duration and number of pain sites are used to calculate a risk score, which indicates the likelihood of a patient having pain in the future. The consistency of a prognostic definition with the concept of integrated patient care was also considered. FINDINGS: When this method was compared with the number of pain days experienced over the previous 6 months--in patients with back pain, headache or orofacial pain--it was a better predictor of clinically significant pain 6 months later for all three pain conditions. Further evidence supporting this approach is that several factors other than the duration of pain have been shown to be important prognostic indicators, including unemployment, functional disability, anxiety and self-rated health. The use of a multifactorial risk score may also suggest specific measures to improve outcomes, such as addressing emotional distress. These measures should be undertaken as part of an integrated pain management strategy; chronic pain is a biopsychosocial phenomenon and all aspects of the patient's pain must be dealt with appropriately and simultaneously for treatment to be effective. CONCLUSION: The implementation of a prognostic definition and wider adoption of integrated care could bring significant advantages. However, these measures require improved training in pain management and structural revision of specialist facilities, for which political support is essential.

Make a CHANGE: optimising communication and pain management decisions.

The major objectives of the CHANGE PAIN International Advisory Board are to enhance understanding of chronic pain and to develop strategies for improving pain management. At its second meeting, in November 2009, evidence was presented that around one person in five in Europe and the USA experiences chronic pain, and the delay before referral to a pain specialist is often several years. Moreover, physicians' pharmacological approach to chronic pain is inconsistent, as evidenced by the huge variation in treatment between different European countries. It was agreed that efficient communication between physician and patient is essential for effective pain management, and that efficacy/side-effect balance is a key factor in choosing an analgesic agent. The multifactorial nature of chronic pain produces various physical and psychological symptoms, so the management of chronic pain should be tailored to the individual. Pharmacological therapy must be matched to the causative mechanisms responsible, or it is likely to prove ineffective and risk the development of a 'vicious circle'; doses are increased because of inadequate pain relief, but this increases side-effects so doses are reduced, pain relief is then inadequate, so doses are increased, and so on. Pain management decisions should not therefore be based solely on the severity of pain. Based on the concept of individual treatment targets (ITT), the CHANGE PAIN Scale was adopted - a simple, user-friendly assessment tool to improve communication between physician and patient. The 11-point NRS enables the patient to rate the current pain intensity and to set a realistic individual target level. On the reverse are six key parameters affecting the patient's quality of life; clinicians simply need to agree with patients whether improvement is needed in each one. Regular use can establish the efficacy and tolerability of pain management, and the rate of progress towards individual treatment targets.