Enhancing Substrate-Metal Catalyst Affinity via Hydrogen Bonding: Pd(II)-Catalyzed ß-C(sp3)-H Bromination of Free Carboxylic Acids.

The achievement of sufficient substrate-metal catalyst affinity is a fundamental challenge for the development of synthetically useful C-H activation reactions of weakly coordinating native substrates. While hydrogen bonding has been harnessed to bias site selectivity in existing C(sp2)-H activation reactions, the potential for designing catalysts with hydrogen bond donors (HBDs) to enhance catalyst-substrate affinity and, thereby, facilitate otherwise unreactive C(sp3)-H activation remains to be demonstrated. Herein, we report the discovery of a ligand scaffold containing a remote amide motif that can form a favorable meta-macrocyclic hydrogen bonding interaction with the aliphatic acid substrate. The utility of this ligand scaffold is demonstrated through the development of an unprecedented C(sp3)-H bromination of α-tertiary and α-quaternary free carboxylic acids, which proceeds in exceedingly high mono-selectivity. The geometric relationship between the NHAc hydrogen bond donor and the coordinating quinoline ligand is crucial for forming the meta-macrocyclophane-like hydrogen bonding interaction, which provides a guideline for the future design of catalysts employing secondary interactions.

Sequential rupture of two concomitant cerebral aneurysms.

The diagnosis of multiple cerebral aneurysms in patients with a spontaneous aneurysmal subarachnoid haemorrhage is not uncommon. The incidence of rupture from a second aneurysm, whilst the patient is recovering from a first bleed is however extremely rare. We report a 21-year-old female with a WFNS grade 1 subarachnoid haemorrhage secondary to a ruptured 5mm right posterior communicating artery aneurysm which was secured with clipping. Sixteen days later, whilst an in-patient, she suffered a second SAH from a left anterior choroidal artery aneurysm which was subsequently coiled. Comparison of digital subtraction angiography showed an almost doubling of the aneurysm from 2.7x2 mm to 4.4x2.3 mm. We review the literature of previously reported simultaneous and sequential aneurysmal subarachnoid haemorrhage and add to the sparse literature on this rare phenomena.

Scurvy: Rare Orthopaedic Complications Associated with Multinutritional Deficiencies.

Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae. Deficiencies of vitamin C, vitamin B3 (niacin) and zinc levels contribute to reduced bone density. Vitamin C associated vertebral fractures, although rare in adults, are still treatable if diagnosed early with a thorough clinical and nutritional history, and early supplementation. Radiological clues suggestive of scurvy-induced vertebral fractures can be diagnosed on plain X-ray and MRI spine imaging. LEARNING POINTS: Although nutritional deficits like scurvy, pellagra and zinc deficiency are rare, early recognition and prompt treatment can prevent critical neurological sequelae.Clinical history including nutritional intake and associated patient symptoms are vital to diagnose scurvy-related vertebral fractures, which are treatable.It is important to note that scurvy can also present in an adult population.

Clinical Reasoning: A 68-Year-Old Man With Palmar Rash, Leg Pain, and Inability to Walk.

We report a 68-year-old man with palmar rash, leg pain, and inability to walk, whose neurologic examination localized to multiple roots, leading to the diagnosis of polyradiculopathy. Polyradiculopathy has both structural and nonstructural etiologies. Structural etiologies include spinal stenosis, tethered cord syndrome, tumors, and leptomeningeal metastasis. Nonstructural etiologies include inflammatory, infectious, metabolic, and other neoplastic processes. His palmar rash in conjunction with neurologic signs/symptoms raised the suspicion for an infectious etiology, and eventually, serology and lumbar puncture confirmed the final diagnosis. In this report, we will further discuss how we determined the localization of polyradiculopathy, its specific etiologies, management decisions, and a transient complication before he achieved a significant improvement at 6 months.

Risk Factors for Syphilis at a Large Urban Emergency Department.

BACKGROUND: The prevalence of syphilis is increasing in the United States. The emergency department (ED) is an important setting to screen and treat underserved populations. To tailor testing protocols to the local population, we aimed to identify risk factors for syphilis positivity in ED patients. METHODS: We performed a retrospective analysis of ED patients who were screened for syphilis between November 2018 and August 2020. Patients were screened for Treponema pallidum antibody using a multiplex flow immunoassay, and positive results were confirmed by rapid plasma reagin or T. pallidum particle agglutination. Risk factors for new syphilis diagnoses were identified using multiple logistic regression. RESULTS: We screened 1974 patients for syphilis (mean age, 37 ± 16 years; 56% female). We identified 201 patients with new infections without previous treatment. Independent risk factors for a new diagnosis of syphilis included housing status (undomiciled, 23% [60 of 256]; domiciled, 9% [133 of 1559]; adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.2-3.0]), history of HIV (positive, 44% [28 of 63]; negative, 9% [173 of 1893]; aOR, 5.8 [95% CI, 3.0-11.2]), tobacco use (positive, 15% [117 of 797]; negative, 4% [29 of 665]; aOR, 2.4 [95% CI, 1.5-3.9]), and illicit drug use (positive, 14% [112 of 812]; negative, 8% [52 of 678]; aOR, 2.2 [95% CI, 1.0-2.5]). CONCLUSIONS: Undomiciled housing status, history of HIV, history of tobacco use, and history of illicit drug use were independently associated with a new diagnosis of syphilis in the ED. Broadening targeted syphilis screening algorithms beyond sexually transmitted disease-related complaints could help identify new syphilis cases for treatment.

Intracranial infected collections and epidemiology in the top end, Northern Territory, Australia. A 10-year case series.

BACKGROUND: The incidence of intracranial infected collections (IIC) ranges between 0.4 and 1.2/100 000 persons per year. There is anecdotal evidence that residents in Top End of the Northern Territory are at a greater risk of infections with protracted clinical presentations. To our knowledge, there is no study to date to explore IIC in the Top End. METHODS: Retrospective observational analysis of IIC in the Top End, Northern Territory, Australia from 2009 to 2019. International classification of disease code G06 was used to identify cases diagnosed at Royal Darwin, Gove District and Katherine Hospital with no restriction of age or gender. RESULTS: A total of 51 cases were identified. This equated to an incidence of 2.9 (95% CI 2.2-3.8) in 100 000 PPY. When separated into Indigenous and non-Indigenous populations, the respective incidences were 8.65 (95% CI 6.2-12.1) and 1.1 (95% CI 0.7-1.9) in 100 000 PPY. The Indigenous population was at a significantly higher risk of IIC compared with non-Indigenous Australians with a relative risk of 7.3 (P < 0.0001 95% CI 4.0-13.3). The most common aetiology was otogenic infections with all cases being identified in the Indigenous population. Comparison of other clinical parameters between the two populations were not statistically significant. CONCLUSIONS: Within the limitations of a retrospective study, the incidence of IICs is higher in the Top End than reported elsewhere in the literature. This is particularly true for the Indigenous population.

Robust Olefin Metathesis Catalyst Bearing a Tridentate Hemilabile NHC Ligand.

An olefin metathesis catalyst bearing a tridentate hemilabile N-heterocyclic carbene (NHC) ligand was synthesized and characterized. The solid-state crystal structure reveals coordination from all three donation sites of the NHC ligand, giving rise to a stable 18-electron complex. Catalytic activity in three standard metathesis reactions was demonstrated, revealing our catalyst to be particularly long lived and highly selective in the self-metathesis of 1-decene. Although the catalyst in this work initiates more slowly than its second-generation counterparts, it was shown to have high thermal stability, yielding peak performances at higher temperatures. The unique ligand framework of this catalyst may serve as a template for the synthesis of analogous catalysts with improved efficiencies.

Septic arthritis of the lumbar facet joint. Case and literature review.

Septic Arthritis of the facet joint (SAFJ) is an uncommon but severe condition of the spine with only 61 cases published to date. Diagnosis is notoriously difficult and can take several months which can lead to significant delays in treatment. We report a case of a 52-year-old female with 2-month history of back pain diagnosed with septic arthritis of the left lumbar L4/5 facet joint and associated epidural abscess. She presented with no fevers, normal neurological examination and normal blood parameters posing a diagnostic challenge. In this report we conclude normal inflammatory markers cannot be used as exclusion criteria for the disease. We also review the body of literature to summarise the key features of the condition to assist clinicians in its diagnosis.

Check the Ear. The Importance of Ear Examinations in Assessment of Intracranial Subdural Empyema.

Intracranial subdural empyema (ISE) is an uncommon condition previously associated with almost 100% morbidity and mortality. Since the introduction of antibiotics and advancements in diagnosis the complication rates have significantly improved. We report an unusual case of a 32-year-old Aboriginal male diagnosed with ISE. On closer inspection the ISE was found to be a complication of otitis media with a cotton bud lodged in the external acoustic meatus. The report provides a literature review on the relationships of ISE, otitis media and foreign bodies. We conclude that although rare, all patients with suspected ISE should undergo an ear examination as it is at no cost to the patient or health service but may be the difference between life and death.

Ultrasensitive Detection of Clostridioides difficile Toxins in Stool by Use of Single-Molecule Counting Technology: Comparison with Detection of Free Toxin by Cell Culture Cytotoxicity Neutralization Assay.

Laboratory tests for Clostridioides difficile infection (CDI) rely on the detection of free toxin or molecular detection of toxin genes. The Singulex Clarity C. diff toxins A/B assay is a rapid, automated, and ultrasensitive assay that detects C. difficile toxins A and B in stool. We compared CDI assays across two prospective multicenter studies to set a cutoff for the Clarity assay and to independently validate the performance compared with that of a cell culture cytotoxicity neutralization assay (CCCNA). The cutoff was set by two sites testing fresh samples from 897 subjects with suspected CDI and then validated at four sites testing fresh samples from 1,005 subjects with suspected CDI. CCCNA testing was performed at a centralized laboratory. Samples with discrepant results between the Clarity assay and CCCNA were retested with CCCNA when the Clarity result agreed with that of at least one comparator method; toxin enzyme immunoassays (EIA), glutamate dehydrogenase (GDH) detection, and PCR were performed on all samples. The cutoff for the Clarity assay was set at 12.0 pg/ml. Compared to results with CCCNA, the Clarity assay initially had 85.2% positive agreement and 92.4% negative agreement. However, when samples with discrepant results between the Clarity assay and CCCNA in the validation study were retested by CCCNA, 13/17 (76.5%) Clarity-negative but CCCNA-positive samples (Clarity+/CCCNA-) became CCCNA-, and 5/26 (19.2%) Clarity+/CCCNA- samples became CCCNA+, resulting in a 96.3% positive agreement and 93.0% negative agreement between Clarity and CCCNA results. The toxin EIA had 59.8% positive agreement with CCCNA. The Clarity assay was the most sensitive free-toxin immunoassay, capable of providing CDI diagnosis in a single-step solution. A different CCCNA result was reported for 42% of retested samples, increasing the positive agreement between Clarity and CCCNA from 85.2% to 96.3% and indicating the challenges of comparing free-toxin results to CCCNA results as a reference standard.

Non missile penetrating spinal injury.

Non-missile penetrating spinal injury (NMPSI) is a rare form of traumatic spinal injury. Cases with neurological deficit on presentation are treated surgically. In the extremely rare circumstance of NMPSI presenting with no neurological deficit the management is contentious. We report a case of a 43-year-old male presenting with a penetrating stab injury through the thoracolumbar spinal canal. On presentation he had no neurological deficits and subsequently the knife was removed in theatre without deep surgical exploration. In this report we review the literature of non-missile penetrating spinal injuries as well as their management and conclude that exploratory surgery for NMPSI without neurological deficit may not be necessary as previously thought.

Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema.

PURPOSE: To evaluate the efficacy of micropulse laser in the early treatment of diabetic macular edema (DME) and its associated burden of anti-vascular endothelial growth factor (VEGF) injections. METHODS: This retrospective comparative study compared a group of 19 eyes with DME treated with micropulse laser to a matched control group of 19 eyes with DME treated with ranibizumab injections without micropulse laser. Recorded parameters included previous medical and ocular history, previous and subsequent ranibizumab injections administered for DME, visual acuity (VA), central macular thickness throughout the follow-up period, and the occurrence of any complications. RESULTS: The improvement in VA was comparable in both groups, at 12 months and at the final follow-up. Patients treated with micropulse laser required significantly fewer ranibizumab injections than their controls, both at 12 months (1.7 ± 2.3 vs 5.6 ± 2.1) and by the end of the follow-up (2.6 ± 3.3 vs 9.3 ± 5.1) (p<0.001 for both). No complications related to the micropulse laser were encountered. CONCLUSIONS: Micropulse laser is a safe and effective treatment for DME, which may achieve comparable improvement in VA along with a significant reduction in the burden of anti-VEGF injections. We suggest a treatment approach for its inclusion in the early stages of DME.

Achilles tendon biomechanics in response to acute intense exercise.

Achilles tendinopathy is a common disorder and is more prevalent in men. Although differences in tendon mechanics between men and women have been reported, understanding of tendon mechanics in young active people is limited. Moreover, there is limited understanding of changes in tendon mechanics in response to acute exercise. Our purpose was to compare Achilles tendon mechanics in active young adult men and women at rest and after light and strenuous activity in the form of repeated jumping with an added load. Participants consisted of 17 men and 14 women (18-30 years) who were classified as being at least moderately physically active as defined by the International Physical Activity Questionnaire. Tendon force/elongation measures were obtained during an isometric plantarflexion contraction on an isokinetic dynamometer with simultaneous ultrasound imaging of the Achilles tendon approximate to the soleus myotendinous junction. Data were collected at rest, after a 10-minute treadmill walk, and after a fatigue protocol of 100 toe jumps performed in a Smith machine, with a load equaling 20% of body mass. We found greater tendon elongation, decreased stiffness, and lower Young's modulus only in women after the jumping exercise. Force and stress were not different between groups but decreased subsequent to the jumping exercise bout. In general, women had greater elongation and strain, less stiffness, and a lower Young's modulus during plantarflexor contraction. These data demonstrate differences in tendon mechanics between men and women and suggest a potential protective mechanism explaining the lower incidence of Achilles tendinopathy in women.