Treatment for TB is lengthy and toxic, and new regimens are needed.
Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg ...moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa
MZ) or 4 months (4Pa
MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa
MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.
Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa
MZ, 4Pa
MZ, 4Pa
MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa
MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.
PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.
Endometriosis is one of the most common gynecological diseases and affects ~10% of women in reproductive age. The most common clinical signs of endometriosis are menstrual irregularities, chronic ...pelvic pain (CPP), dysmenorrhea, dyspareunia and infertility. Symptoms of endometriosis often affect psychological and social functioning of patients. For this reason, endometriosis is considered as a disabling condition that may significantly compromise social relationships, sexuality and mental health. Considering this point, the aim of this narrative review is to elucidate the impact of anxiety and depression in the management of women with endometriosis. Psychological factors have an important role in determining the severity of symptoms, and women who suffer from endometriosis report high levels of anxiety, depression and other psychiatric disorders. In addition, endometriosis is one of the most important causes of CPP; women with endometriosis suffer from a wide range of pelvic pain such as dysmenorrhea, dyspareunia, nonmenstrual (chronic) pelvic pain, pain at ovulation, dyschezia and dysuria. Several studies have underlined the influence of CPP on quality of life and psychological well-being of women with endometriosis. Data suggest that the experience of pelvic pain is an important component of endometriosis and may significantly affect emotive functioning of affected women. It has been demonstrated that high levels of anxiety and depression can amplify the severity of pain. Further studies are needed to better understand the relationship between psychological factors and perception of pain. Treatment of endometriosis may be hormonal or surgical. Surgery is the primary treatment for more severe forms of endometriosis. There are few data in the literature about the influence of psychological factors and psychiatric comorbidities on the effectiveness of treatments. It is important to evaluate the presence of previous psychiatric diseases in order to select the most appropriate treatment for the patient.
Purpose
Postamputation pain is challenging because of complex mechanisms involving a multitude of pain pathways and psychological factors. This patient population also tends to have extensive ...comorbidities with or without a background of chronic pain. Electrical neuromodulation such as peripheral nerve stimulation has gained traction in the realm of chronic pain. Recently, the off-label use of hybrid perineural nerve stimulation in combination with locoregional block via the stimulating nerve block catheter has been described in single-center case reports.
Clinical features
Herein, we present a case series of six patients from two different Canadian hospitals using such a hybrid technique in three different clinical scenarios. These scenarios were (1) local anesthetic dose minimization in the presence of multiple nerve block catheters, (2) analgesia augmentation when local anesthetic alone is insufficient, and (3) provision of an analgesic adjunct as part of a multimodal regimen. A stimulating sciatic nerve block catheter was inserted under ultrasound and nerve stimulation guidance for these cases. Patients tended to experience pain on the subsequent postoperative days whereby the off-label use of nerve stimulation successfully reduced their pain score and stabilized or decreased their opioid consumption or minimized the need to increase the local anesthetic dose when doing so could have precipitated local anesthetic toxicity.
Conclusion
Our case series supports the feasibility of using a combination of low-frequency perineural stimulation and local anesthetic infusion via a single perineural nerve block catheter to manage challenging postamputation pain.
While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after ...spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.
The risk of bleeding complications during regional anesthesia procedures is a significant patient safety consideration. Nevertheless, existing literature provides limited guidance on the ...stratification of bleeding risk for peripheral nerve and newly described interfascial plane blocks. Our objective was to produce an evidence-based consensus advisory that classifies bleeding risks in patients undergoing regional peripheral nerve and interfascial plane block procedures. This advisory is intended to facilitate clinical decision-making in conjunction with national or local guidelines and to guide consideration for appropriate alterations to anticoagulation regimens before specific regional anesthesia procedures. In pursuit of this goal, the Regional Anesthesia and Acute Pain Section of the Canadian Anesthesiologists Society (CAS) assembled a panel of seven Canadian experts to classify the risk of bleeding complications associated with regional peripheral nerve and interfascial plane blocks. At the 75
th
annual meeting of the CAS in June 2018, the panel’s expert opinion was finalized and the published literature was quantified within an organized framework. All common peripheral nerve and interfascial plane blocks were categorized into “low risk”, “intermediate risk”, and “high risk” based on the literature evidence, bleeding risk scores, and consensus opinion (in that order of priority). Clinical data is often limited, so readers of this consensus report should be reminded that these recommendations are mostly based on expert consensus. Hence, this advisory should not to be defined as a standard of care but rather serve as a resource for clinicians assessing the risk and benefits of regional anesthesia in management of their patients.
The MEG II experiment, based at the Paul Scherrer Institut in Switzerland, reports the result of a search for the decay
μ
+
→
e
+
γ
from data taken in the first physics run in 2021. No excess of ...events over the expected background is observed, yielding an upper limit on the branching ratio of
B
(
μ
+
→
e
+
γ
)
<
7.5
×
10
-
13
(90% CL). The combination of this result and the limit obtained by MEG gives
B
(
μ
+
→
e
+
γ
)
<
3.1
×
10
-
13
(90% CL), which is the most stringent limit to date. A ten-fold larger sample of data is being collected during the years 2022–2023, and data-taking will continue in the coming years.
We report on a search for ultralow-mass axionlike dark matter by analyzing the ratio of the spin-precession frequencies of stored ultracold neutrons and Hg199 atoms for an axion-induced oscillating ...electric dipole moment of the neutron and an axion-wind spin-precession effect. No signal consistent with dark matter is observed for the axion mass range 10−24≤ma≤10−17eV . Our null result sets the first laboratory constraints on the coupling of axion dark matter to gluons, which improve on astrophysical limits by up to 3 orders of magnitude, and also improves on previous laboratory constraints on the axion coupling to nucleons by up to a factor of 40.
Abstract
Functional conductive hydrogels are widely used in various application scenarios, such as artificial skin, cell scaffolds, and implantable bioelectronics. However, their novel designs and ...technological innovations are severely hampered by traditional manufacturing approaches. Direct ink writing (DIW) is considered a viable industrial‐production 3D‐printing technology for the custom production of hydrogels according to the intended applications. Unfortunately, creating functional conductive hydrogels by DIW has long been plagued by complicated ink formulation and printing processes. In this study, a highly 3D printable poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)‐based ink made from fully commercially accessible raw materials is demonstrated. It is shown that complex structures can be directly printed with this ink and then precisely converted into high‐performance hydrogels via a post‐printing freeze–thawing treatment. The 3D‐printed hydrogel exhibits high electrical conductivity of ≈2000 S m
−1
, outstanding elasticity, high stability and durability in water, electromagnetic interference shielding, and sensing capabilities. Moreover, the hydrogel is biocompatible, showing great potential for implantable and tissue engineering applications. With significant advantages, the fabrication strategy is expected to open up a new route to create multifunctional hydrogels with custom features, and can bring new opportunities to broaden the applications of hydrogel materials.
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