Review of Malaysian medicinal plants with potential wound healing activity.

Wound is defined as the damage to biological tissues including skin, mucous membranes and organ tissues. The acute wound heals in less than 4 weeks without complications, while a chronic wound takes longer than 6 weeks to heal. Wound healing occurs in 4 phases, namely, coagulation, inflammatory, proliferative and remodeling phases. Triclosan and benzalkonium chloride are commonly used as skin disinfectants in wound healing. However, they cause allergic contact dermatitis and antibiotic resistance. Medicinal plants are widely studied due to the limited availability of wound healing agents. The present review included six commonly available medicinal plants in Malaysia such as Aloe barbadensis Miller, Carica papaya Linn., Centella asiatica Linn., Cymbopogon nardus Linn., Ficus benghalensis Linn. and Hibiscus rosa sinensis Linn. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PubMed Central and Research Gate. The review discussed the possible mechanism of action of medicinal plants and their active constituents in the wound healing process. In addition, their application in nanotechnology and wound dressings was also discussed in detail.

Radial sclerosing lesions found on core needle biopsy: excision can be safely avoided.

AIMS: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. METHODS AND RESULTS: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. CONCLUSIONS: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia.

Approximately 50% of acute intestinal failure (AIF) patients on short-term parenteral nutrition (PN) have intestinal failure-associated liver disease (IFALD) without effect on hospital length of stay and mortality.

INTRODUCTION: Patients with intestinal failure (IF) are often dependent on PN for provision of calories and nutrients for survival. Similar to chronic intestinal failure (CIF) patients, those who have AIF are also at risk of IFALD, which is a poorly understood but potentially fatal condition. The local incidence of IFALD amongst AIF patients is not known. OBJECTIVES: The primary objective of this study was to determine the incidence of IFALD in AIF patients on short-term PN. Secondary objectives were to analyse patient and PN risk factors of IFALD, and clinical outcomes of length of stay (LOS) and inpatient mortality. DESIGN: This was a retrospective cross-sectional cohort study of hospitalised adult patients with AIF prescribed with short-term PN. All adult patients aged 21 years and above who received PN for at least 5 consecutive days and had normal liver function tests (LFTs) at the time of PN initiation were included in this study. RESULTS: A total of 171 patients were enrolled in this study, with 77 (45%) having deranged LFTs at the end of PN therapy and categorised under the IFLAD group. The patient cohort was predominantly male (92 [54%]) and had a median age of 68 years (IQR 59-76). Patients with IFALD at the end of PN therapy had higher diabetes prevalence (36% vs 26%, p = 0.2) and were on PN for a longer duration (median [IQR]: 12 [8-17] vs 8 [6-15] days, p = 0.003) than those without IFALD. There were no significant differences in patient and PN characteristics between the IFLAD and non-IFALD group. The multivariable models showed that the IFALD cohort had longer hospital stays (HR 0.90, 95% CI 0.65-1.23) and lower odds of inpatient death (OR 0.75, 95% CI 0.12-4.60), though both findings are not statistically significant (p = 0.5, 0.7). CONCLUSION: In this study, IFALD is a common phenomenon in AIF and the incidence was found to be an estimated 50% amongst patients on short-term PN with similar clinical outcomes between the two groups.

US of the Penis: Beyond Erectile Dysfunction.

High-frequency US, with a linear transducer and gray-scale, color, and spectral Doppler US techniques, is the primary imaging modality for evaluation of the penis. It can allow delineation of anatomy and assessment of dynamic blood flow; it is easily available and noninvasive or minimally invasive; it is cost effective; and it is well tolerated by patients. US assessment after pharmacologic induction of erection is an additional tool in assessing patients with suspected vasculogenic impotence, and also in selected patients with penile trauma and suspected Peyronie disease. Penile injuries, life-threatening infections, and vascular conditions such as priapism warrant rapid diagnosis to prevent long-term morbidities due to clinical misdiagnosis or delayed treatment. US can facilitate a timely diagnosis in these emergency conditions, even at the point of care such as the emergency department, which can facilitate timely treatment. In addition, color and spectral Doppler US are valuable applications in the follow-up of patients treated with endovascular revascularization procedures for vasculogenic erectile dysfunction. Image optimization and attention to meticulous techniques including Doppler US is vital to improve diagnostic accuracy. Radiologists should be familiar with the detailed US anatomy, pathophysiologic characteristics, scanning techniques, potential pitfalls, and US manifestations of a wide spectrum of vascular and nonvascular penile conditions to suggest an accurate diagnosis and direct further management. The authors review a range of common and uncommon abnormalities of the penis, highlight their key US features, discuss differential diagnosis considerations, and briefly review management. ©RSNA, 2024 Supplemental material is available for this article.

Application of Cas12j for Streptomyces Editing.

In recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Streptococcus pyogenes Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of Streptomyces strains. This study explored the first use of Acidaminococcus sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in Streptomyces and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previously reported efficiencies of Cas12a and Cas9, Cas12j exhibited higher transformation efficiencies compared to SpCas9. Furthermore, Cas12j demonstrated significantly improved editing efficiencies compared to Cas12a in activating BGCs in Streptomyces sp. A34053, a strain wherein both SpCas9 and Cas12a faced limitations in accessing the genome. Overall, this study expanded the repertoire of Cas proteins for genome editing in actinomycetes and highlighted not only the potential of recently characterized Cas12j in Streptomyces but also the importance of having an extensive genetic toolbox for improving the editing success of these beneficial microbes.

Use of minimally invasive ultrasound transducer during tubular microdiscectomy.

Minimally invasive ultrasound during tubular microdiscectomy is novel. The authors report the technique during surgery for L5-S1 herniated disc. Ultrasound provided real-time visualization of the pathology and neural elements. After discectomy and tactile assessment, ultrasound showed decompression of the thecal sac and traversing nerve root. The patient tolerated the procedure well, with resolution of preoperative pain and strength improvement. Postoperative MRI revealed a residual asymptomatic disc fragment that was retrospectively identified on ultrasonography. Minimally invasive ultrasound could become a useful supplement to direct visual and tactile assessment during tubular microdiscectomy, but further experience with surgical anatomy on ultrasound is required. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23206.

Real-Time Ultrasound-Guided Posterolateral Thoracic Discectomy: 2-Dimensional Operative Video.

Symptomatic thoracic disk herniations can be challenging to treat. Various surgical approaches have been reported in the literature, but the ideal approach is still a topic of controversy. We present a step-by-step surgical video highlighting the utilization of continuous, real-time intraoperative ultrasound (IOUS) guidance for thoracic discectomy through a posterolateral approach. The background and rationale for the procedure and a detailed presentation of the sequence of surgical steps are detailed in the operative video. We believe that real-time IOUS can be used not only to gain an understanding of the ventral anatomy and to verify decompression after discectomy but it can also be used in a real-time fashion to guide the maneuvers for discectomy itself. Advantages of using real-time IOUS include real-time monitoring of the spinal cord during mobilization of the disk-osteophyte complex and direct visualization of the dura-disk herniation interface, which may enhance the safety of surgery. The patient consented to the procedure and the publication of her image.

Real-Time Intraoperative Ultrasound Using a Minimally Invasive Transducer During Anterior Cervical Spine Surgery.

BACKGROUND AND OBJECTIVES: Intraoperative ultrasound (IOUS) during anterior cervical surgery is hindered by large transducer size and small operative corridor. We hypothesized that a linear (minimally invasive) transducer designed for transsphenoidal surgery can visualize the spinal cord, nerve roots, and surrounding structures during anterior cervical approaches, facilitating intraoperative assessment of central and foraminal decompression. METHODS: IOUS was used to evaluate 26 levels in 17 patients (15 anterior cervical discectomy and fusion, 1 corpectomy, 1 arthroplasty) with a linear probe (7 × 6-mm end-fire transducer, 150-mm length, 12-15 MHz). After pin-based distraction, discectomy, and posterior longitudinal ligament resection, IOUS assessed adequacy of cord decompression and, following proximal foraminotomy or uncinectomy, nerve root decompression. If indicated, additional decompression was completed. Criteria for adequate central and foraminal decompression were visualization of subarachnoid space around the cord and cerebrospinal fluid pulsatility along the root sleeve/absence of nerve root compression distal to the root sleeve, respectively. RESULTS: IOUS successfully visualized the cord, nerve roots, and surrounding structures in all 26 levels and influenced management in 11 levels (42.3%). IOUS indicated persistent cord and nerve root compression in 2 and 7 levels, respectively. Planned uncinectomy was aborted in 2 levels after IOUS demonstrated adequate nerve root decompression with intervertebral distraction/proximal foraminotomy alone. IOUS identified persistent nerve root compression after initial proximal foraminotomy in 4 levels and uncinectomy in 2 levels. An unplanned uncinectomy was performed in 1 level after IOUS showed persistent nerve root compression after multiple iterations of proximal foraminotomy. At follow-up (mean 3.1 months), the mean improvement in Numeric Rating Scale neck and arm pain, Neck Disability Index, and modified Japanese Orthopedic Association was 4.0%, 3.2%, 3.7%, and 0.7%, respectively. CONCLUSION: The neural elements and their relationships to surrounding bone/soft tissue can be visualized using a minimally invasive IOUS transducer during anterior cervical surgery without having to remove pin-based distraction. This allows surgeons to intraoperatively verify the extent of central and foraminal decompression.

Intravenous methylprednisolone-induced hypokalaemic periodic paralysis in a thyrotoxic patient: a case report and literature review.

Hypokalaemic periodic paralysis (HPP) is an uncommon complication of corticosteroid therapy, which may also be seen in thyrotoxicosis. It was mostly described in the Asian population, and it is rare in other ethnic groups. We present the case of a poorly controlled thyrotoxic Caucasian male with thyroid eye disease (TED) who suffered an acute quadriplegic episode caused by severe hypokalaemia and was admitted to the intensive care unit (ITU) within 24 hours of initiating intravenous methylprednisolone (IVMP) infusion. Once his potassium blood levels were repleted, he completely recovered from the episode. Although HPP is rare in the Caucasian population, it can be precipitated in thyrotoxic patients by systemic steroids. Caution should be exercised when administering IVMP in poorly controlled thyrotoxic patients, and we suggest monitoring the potassium levels at regular intervals with ECG monitoring for at least 24 hours in at-risk individuals.

Site-selective chlorination of pyrrolic heterocycles by flavin dependent enzyme PrnC.

Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil.

Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.

Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.

Parenteral nutrition-related complications in older patients with acute intestinal failure: A descriptive cohort study.

INTRODUCTION: Reported outcomes for parenteral nutrition (PN)-related complications in older adult patients with acute intestinal failure who are receiving PN in the acute hospital setting are limited. Our study aims to compare PN-related complications between older and younger adult patients. METHODS: A retrospective descriptive study of inpatients who were administered PN from January 1, 2019, to December 31, 2019, was performed. Patients were categorized into older (≥65 years old) and younger (<65 years old) adult groups. RESULTS: Two hundred thirty-five patients were included. There were 103 patients in the older adult group (mean age: 73.9 [SD: 6.9] years) and 132 patients in the younger adult group (mean age: 52.4 [SD: 12.5] years). There was a significantly higher Charlson Comorbidity Index score and lower Karnofsky score in the older adult group. The older adult group received significantly lower total energy (20.8 [SD: 7.8] vs 22.8 [SD: 6.3] kcal/kg/day), dextrose (3.1 [SD: 1.4] vs 3.6 [SD: 1.4] g/kg/day), and protein (1.1 [SD: 0.4] vs 1.2 [SD: 0.3] g/kg/day) than the younger group received. The mean length of stay was significantly shorter in the older adult group (35.9 [SD: 21.3] vs 59.8 [SD: 55.3]; P < 0.05). There was no significant difference in PN-related complications and clinical outcomes (catheter-related bloodstream infections, hypoglycemia or hyperglycemia, fluid overload, or inpatient mortality) between the two groups. CONCLUSION: Despite more comorbidities in the older adult, the usage of PN in older adult patients with acute intestinal failure was associated with neither an increased rate of PN-related complications nor worse clinical outcomes when compared with that of younger patients.

Risk factors for C5 palsy: a systematic review and multivariate analysis.

OBJECTIVE: Postoperative C5 palsy (C5P) is a known complication in cervical spine surgery. However, its exact pathophysiology is unclear. The authors aimed to provide a review of the current understanding of C5P by performing a comprehensive, systematic review of the existing literature and conducting a critical appraisal of existing evidence to determine the risk factors of C5P. METHODS: A systematic search of PubMed/MEDLINE (January 1, 2019, to July 2, 2021), EMBASE (inception to July 2, 2021), and Cochrane (inception to July 2, 2021) databases was conducted. Preestablished criteria were used to evaluate studies for inclusion. Studies that adjusted for one or more of the following factors were considered: preoperative foraminal diameter (FD) at C4/5, posterior spinal cord shift at C4/5, preoperative anterior-posterior diameter (APD) at C4/5, preoperative spinal cord rotation, and change in C2-7 Cobb angle. Studies were rated as good, fair, or poor based on the Quality in Prognosis Studies (QUIPS) tool. Random effects meta-analyses were done using methods outlined by Cochrane methodologists for pooling of prognostic studies. Overall quality (strength) of evidence was based on Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods for prognostic studies. The protocol for this review was published on the PROSPERO (CRD264358) website. RESULTS: Of 303 potentially relevant citations of studies, 12 met the inclusion criteria set a priori. These works provide moderate-quality evidence that preoperative FD substantially increases the odds of C5P in patients undergoing posterior cervical surgery. Pooled estimates across 7 studies in which various surgical approaches were used indicate that the odds of C5P approximately triple for each millimeter decrease in preoperative FD (OR 3.05, 95% CI 2.07-4.49). Preoperative APD increases the odds of C5P, but the confidence is low. Across 3 studies, each using different surgical approaches, each millimeter decrease in preoperative APD was associated with a more than 2-fold increased odds of C5P (pooled OR 2.51, 95% CI 1.69-3.73). Confidence that there is an association with postoperative C5P and posterior spinal cord shift, change in sagittal Cobb angle, and preoperative spinal cord rotation is very low. CONCLUSIONS: The exact pathophysiological process resulting in postoperative C5P remains an enigma but there is a clear association with foraminal stenosis, especially when performing posterior procedures. C5P is also related to decreased APD but the association is less clear. The overall quality (strength) of evidence provided by the current literature is low to very low for most factors. Systematic review registration no.: CRD264358 (https://www.crd.york.ac.uk/prospero/).

Multilevel Laminoplasty for CSM: Is C3 Laminectomy Better Than C3 Laminoplasty at the Superior Vertebra?

INTRODUCTION: In a multilevel cervical laminoplasty operation for patients with cervical spondylotic myelopathy (CSM), a partial or complete C3 laminectomy may be performed at the upper level instead of a C3 plated laminoplasty. It is unknown whether C3 technique above the laminoplasty affects loss of cervical lordosis or range of motion. METHODS: Patients undergoing multilevel laminoplasty of the cervical spine (C3-C6/C7) at a single institution were retrospectively reviewed. Patients were divided into two cohorts based on surgical technique at C3: C3-C6/C7 plated laminoplasty ("C3 laminoplasty only", N = 61), C3 partial or complete laminectomy, plus C4-C6/C7 plated laminoplasty (N = 39). All patients had at least 1-year postoperative X-ray treatment. RESULTS: Of 100 total patients, C3 laminoplasty and C3 laminectomy were equivalent in all demographic data, except for age (66.4 vs. 59.4 years, p = 0.012). None of the preoperative radiographic parameters differed between the C3 laminoplasty and C3 laminectomy cohorts: cervical lordosis (13.1° vs. 11.1°, p = 0.259), T1 slope (32.9° vs. 29.2°, p = 0.072), T1 slope-cervical lordosis (19.8° vs. 18.6°, p = 0.485), or cervical sagittal vertical axis (3.1 cm vs. 2.7 cm, p = 0.193). None of the postoperative radiographic parameters differed between the C3 laminoplasty and C3 laminectomy cohorts: cervical lordosis (9.4° vs. 11.2°, p = 0.369), T1 slope-cervical lordosis (21.7° vs. 18.1°, p = 0.126), to cervical sagittal vertical axis (3.3 cm vs. 3.6 cm, p = 0.479). In the total cohort, 31% had loss of cervical lordosis >5°. Loss of lordosis reached 5-10° (mild change) in 13% of patients and >10° (moderate change) in 18% of patients. C3 laminoplasty and C3 laminectomy cohorts did not differ with respect to no change (<5°: 65.6% vs. 74.3%, respectively), mild change (5-10°: 14.8% vs. 10.3%), and moderate change (>10°: 19.7% vs. 15.4%) in cervical lordosis, p = 0.644. When controlling for age, ordinal regression showed that surgical technique at C3 did not increase the odds of postoperative loss of cervical lordosis. C3 laminectomy versus C3 laminoplasty did not differ in the postoperative range of motion on cervical flexion-extension X-rays (23.9° vs. 21.7°, p = 0.451, N = 91). CONCLUSION: There was no difference in postoperative loss of cervical lordosis or postoperative range of motion in patients who underwent either C3-C6/C7 plated laminoplasty or C3 laminectomy plus C4-C6/C7 plated laminoplasty.

Direct arene trifluoromethylation enabled by promiscuous activity of fungal laccase.

Laccase from Trametes versicolor was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of in situ generated CF3 radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.

Robotic-Assisted Surgery and Navigation in Deformity Surgery.

Deformity surgery is advancing quickly with the use of three-dimensional navigation and robotics. In spinal fusion, the use of robotics improves screw placement accuracy and reduces radiation, complications, blood loss, and recovery time. Currently, there is limited evidence showing that robotics is better than traditional freehand techniques. Most studies favoring robotics are small and retrospective due to the novelty of the technology in deformity surgery. Using these systems can also be expensive and time-consuming. Surgeons should use these advancements as tools, but not rely on them to replace surgical experience, anatomy knowledge, and good judgment.

Enhanced Recovery After Surgery Protocols and Spinal Deformity.

The authors outline a review of preoperative, intraoperative, and postoperative considerations surrounding adult spinal deformity. Preoperative management topics include imaging, hemoglobin A1c levels before spine surgery, osteoporotic management, and prehabilitation. Topics surrounding intraoperative management include the use of antibiotics, liposomal bupivacaine, and Foley catheters. The authors also discuss postoperative questions surrounding analgesia, nausea and vomiting, thromboembolic prophylaxis, and early mobilization. Throughout their discussion, the authors incorporate enhanced recovery after surgery protocols to hopefully lead to future discussions regarding optimizing complex spinal patients.