Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review.  Results: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses.  Conclusions: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties.  J Drugs Dermatol. 2024;23(3):173-186. doi:10.36849/JDD.7243e.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review. RESULTS: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses. CONCLUSIONS: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties. J Drugs Dermatol. 2023;22(9): doi:10.36849/JDD.7243e.

New Noncentrosymmetric Tetrel Pnictides Composed of Square-Planar Gold(I) with Peculiar Bonding.

Three novel isostructural equiatomic gold tetrel pnictides, AuSiAs, AuGeP, and AuGeAs, were synthesized and characterized. These phases crystallize in the noncentrosymmetric (NCS) monoclinic space group Cc (no. 9), featuring square-planar Au within cis-[AuTt2 Pn2 ] units (Tt=tetrel, Si, Ge; Pn=pnictogen, P, As). This is in drastic contrast to the structure of previously reported AuSiP, which exhibits typical linear coordination of Au with Si and P. Chemical bonding analysis through the electron localization function suggests covalent two-center two-electron Tt-Pn bonds, and three-center Au-Tt-Au and Au-Pn-Au bonds with 1.6 e- per bond. X-ray photoelectron spectroscopy studies support the covalent and nonionic nature of Au-Pn and Au-Tt bonds. The title materials were found to be n-type narrow-gap semiconductors or semimetals, with nearly temperature-independent electrical resistivities and low thermal conductivities. A combination of the semimetallic properties with tunable NCS structure provides opportunities for the development of materials based on gold tetrel pnictides.

Directing Boron-Phosphorus Bonds in Crystalline Solid: Oxidative Polymerization of P═B═P Monomers into 1D Chains.

Over 20 years after the last inorganic ternary B-P compound was reported, Na2BP2, a new compound containing one-dimensional B-P polyanionic chains has been synthesized. Common high-temperature synthetic methods required for the direct reaction of boron and phosphorus negate the possible formation of metastable or low temperature phases. In this study, oxidative elimination was used to successfully condense 0D BP23- anionic monomers found in a Na3BP2 precursor into unique 1D BP22- chains consisting of five-member B2P3 rings connected by bridging P atoms in the crystal structure of Na2BP2. The synthesis was guided by in situ X-ray powder diffraction studies, which revealed the metastable nature of the products of oxidative elimination reactions. Na2BP2 is predicted to be an electron balanced semiconductor which was confirmed by UV-vis spectroscopy with the experimentally determined band gap of 1.1 eV.

Ba2Si3P6: 1D Nonlinear Optical Material with Thermal Barrier Chains.

A novel barium silicon phosphide was synthesized and characterized. Ba2Si3P6 crystallizes in the noncentrosymmetric space group Pna21 (No. 33) and exhibits a unique bonding connectivity in the Si-P polyanion not found in other compounds. The crystal structure is composed of SiP4 tetrahedra connected into one-dimensional double-tetrahedra chains through corner sharing, edge sharing, and covalent P-P bonds. Chains are surrounded by Ba cations to achieve an electron balance. The novel compound exhibits semiconducting properties with a calculated bandgap of 1.6 eV and experimental optical bandgap of 1.88 eV. The complex pseudo-one-dimensional structure manifests itself in the transport and optical properties of Ba2Si3P6, demonstrating ultralow thermal conductivity (0.56 W m-1 K-1 at 300 K), promising second harmonic generation signal (0.9 × AgGaS2), as well as high laser damage threshold (1.6 × AgGaS2, 48.5 MW/cm2) when compared to the benchmark material AgGaS2. Differential scanning calorimetry reveals that Ba2Si3P6 melts congruently at 1373 K, suggesting that large single crystal growth may be possible.

Chemical and Electrochemical Lithiation of van der Waals Tetrel-Arsenides.

Lithiation of van der Waals tetrel-arsenides, GeAs and SiAs, has been investigated. Electrochemical lithiation demonstrated large initial capacities of over 950 mAh g-1 accompanied by rapid fading over successive cycling in the voltage range 0.01-2 V. Limiting the voltage range to 0.5-2 V achieved more stable cycling, which was attributed to the intercalation process with lower capacities. Ex situ powder X-ray diffraction confirmed complete amorphization of the samples after lithiation, as well as recrystallization of the binary tetrel-arsenide phases after full delithiation in the voltage range 0.5-2 V. Solid-state synthetic methods produce layered phases, in which Si-As or Ge-As layers are separated by Li cations. The first layered compounds in the corresponding ternary systems were discovered, Li0.9 Ge2.9 As3.1 and Li3 Si7 As8 , which crystallize in the Pbam (No. 55) and P2/m (No. 10) space groups, respectively. Semiconducting layered GeAs and SiAs accommodate the extra charge from Li cations through structural rearrangement in the Si-As or Ge-As layers and eventually by replacement of the tetrel dumbbells with sets of Li atoms. Ge and Si monoarsenides demonstrated high structural flexibility and a mild ability for reversible lithiation.

In-hospital stroke and mortality trends after left ventricular assist device implantation in the United States from 2017 to 2019.

BACKGROUND: The newer Left Ventricular Assist Device (LVAD), the HeartMate 3 (HM3), was initially approved by the Food and Drug Administration in 2017. We aimed to describe the temporal trends of in-hospital stroke and mortality among patients who underwent LVAD placement between 2017 and 2019. METHODS: The National Inpatient Sample was queried from 2017 to 2019 to identify all adults with heart failure and reduced ejection fraction (HFrEF) who underwent LVAD implantation using the International Classification of Diseases 10th Revision codes. The Cochran-Armitage test was conducted to assess the linear trend of in-hospital stroke and mortality. In addition, multivariable regression analysis was conducted to assess the association of LVAD placement with in-hospital stroke and death. RESULTS: A total of 5,087,280 patients met the selection criteria. Of those, 11,750 (0.2%) underwent LVAD implantation. There was a downtrend in in-hospital mortality per year (trend: -1.8%, p = 0.03), but not in the trend of both ischemic and hemorrhagic stroke per year. LVAD placement was associated with greater odds of stroke of any type (OR = 1.96, 95% CI 1.68-2.29, p < 0.001) and in-hospital mortality (OR = 1.37, 95% CI 1.16-1.61, p < 0.001). CONCLUSIONS: Our study found a significant downtrend in the in-hospital mortality rates among patients with LVAD without substantial changes in stroke rate trends over the study timeframe. As stroke rates remained steady, we hypothesize that improved management along with better control of blood pressure, could have played an important role in survival benefit over the study time frame.

The role of targeted temperature management in 30-day hospital readmissions in cardiac arrest survivors: A national population-based study.

Background: Targeted temperature management (TTM) implementation following resuscitation from cardiac arrest is controversial. Although prior studies have shown that TTM improves neurological outcomes and mortality, less is known about the rates or causes of readmission in cardiac arrest survivors within 30 days. We aimed to determine whether the implementation of TTM improves all-cause 30-day unplanned readmission rates in cardiac arrest survivors. Methods: Using the Nationwide Readmissions Database, we identified 353,379 adult cardiac arrest index hospitalizations and discharges using the International Classification of Diseases, 9th and 10th codes. The primary outcome was 30-day all-cause unplanned readmissions following cardiac arrest discharge. Secondary outcomes included 30-day readmission rates and reasons, including impacts on other organ systems. Results: Of 353,379 discharges for cardiac arrest with 30-day readmission, 9,898 (2.80%) received TTM during index hospitalization. TTM implementation was associated with lower 30-day all-cause unplanned readmission rates versus non-recipients (6.30% vs. 9.30%, p < 0.001). During index hospitalization, receiving TTM was also associated with higher rates of AKI (41.12% vs. 37.62%, p < 0.001) and AHF (20.13% vs. 17.30%, p < 0.001). We identified an association between lower rates of 30-day readmission for AKI (18.34% vs. 27.48%, p < 0.05) and trend toward lower AHF readmissions (11.32% vs. 17.97%, p = 0.05) among TTM recipients. Conclusions: Our study highlights a possible negative association between TTM and unplanned 30-day readmission in cardiac arrest survivors, thereby potentially reducing the impact and burden of increased short-term readmission in these patients. Future randomized studies are warranted to optimize TTM use during post-arrest care.

Post-inflammatory Hyperpigmentation in an African American Female: An Atypical Presentation and Treatment Dilemma.

We present the case of a 32-year-old African American female with a known history of primary Sjogren's syndrome, multiple vitamin deficiencies, and prior facial cellulitis who presented with diffuse facial post-inflammatory hyperpigmentation following a motor vehicle accident. Following glucocorticoid treatment, only select hyperpigmented areas associated with inflammation, infection, or trauma improved, which thereby posed a clinical challenge to improve the patient's appearance and condition. Such results may warrant the consideration of adjunctive topical therapies to lighten the remaining areas of hyperpigmentation.

Role of genetic polymorphisms in clopidogrel response variability: a systematic review.

INTRODUCTION: Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease. AREAS COVERED: As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients. EXPERTS' COMMENTARY: Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.

Rare extension of pancreatic pseudocyst with Mycobacterium abscessus into the iliopsoas muscle.

Pancreatic pseudocyst is a well-known complication of both acute and chronic pancreatitis. Although extension into other anatomical sites is common, extension into the retrofascial space causing an iliopsoas abscess is exceedingly rare. Although its low incidence creates a diagnostic challenge for clinicians, early diagnosis is essential to prevent significant complications and poor patient outcomes. We present a case of iliopsoas abscess with unusual culture fluid growth in the setting of acute on chronic pancreatitis secondary to extension of a pancreatic pseudocyst. We also offer a brief review of the literature and pathophysiology of the condition.

Rare Occurrence of a Symptomatic Persistent Sciatic Artery Aneurysm.

Persistent sciatic artery (PSA) aneurysms are a rare cause of gluteal or lower extremity pain. The persistent sciatic artery is an uncommon congenital vasculature anomaly that presents with variable clinical presentation and is prone to cause an aneurysm, thrombosis, rupture, and possible amputation. Thus, early diagnosis is imperative to prevent further complications. We present the case of a 75-year-old female who was diagnosed with a persistent sciatic artery aneurysm after presenting with gluteal and lower extremity pain initially thought to be sciatica. Our patient underwent a successful hybrid open and endovascular approach with a femoral to below-knee popliteal artery bypass and the placement of coils at the proximal and distal ends of the aneurysmal segment.

The Effect of Admission During the Weekend On In-Hospital Outcomes for Patients With Peripartum Cardiomyopathy.

Background Previous studies have shown that patients with heart failure (HF) and cardiogenic shock (CS) have worse outcomes when admitted over the weekend. Since peripartum cardiomyopathy (PPCM) is a cause of CS and persisting HF, it is reasonable to extrapolate that admission over the weekend would also have deleterious effects on PPCM outcomes. However, the impact of weekend admission has not been specifically evaluated in patients with PPCM. Methods We analyzed the National Inpatient Sample (NIS) from 2016 to 2019. The International Classification of Diseases, tenth revision (ICD-10) codes were used to identify all admissions with a primary diagnosis of PPCM. The sample was divided into weekday and weekend groups. We performed a multivariate regression analysis to estimate the effect of weekend admission on specified outcomes. Results A total of 6,120 admissions met the selection criteria, and 25.3% (n=1,550) were admitted over the weekend. The mean age was 31.3 ± 6.4 years. There were no significant differences in baseline characteristics between study groups. After multivariate analysis, weekend admission for PPCM was not associated with in-hospital mortality, ventricular arrhythmias, sudden cardiac arrest, thromboembolic events, cardiovascular implantable electronic device placement, and mechanical circulatory support insertion. Conclusion In conclusion, although HF and CS have been associated with worse outcomes when admitted over the weekend, we did not find weekend admission for PPCM to be independently associated with worse clinical outcomes after multivariate analysis. These findings could reflect improvement in the coordination of care over the weekend, improvement in physician handoff, and increased utilization of shock teams.

Third time's the charm: intricate non-centrosymmetric polymorphism in LnSiP3 (Ln = La and Ce) induced by distortions of phosphorus square layers.

Complex polymorphic relationships in the LnSiP3 (Ln = La and Ce) family of compounds are reported. An innovative synthetic method was developed to overcome differences in the reactivities of the rare-earth metal and refractory silicon with phosphorus. Reactions of atomically mixed Ln + Si with P allowed for selective control over the reaction outcomes resulting in targeted isolation of three new polymorphs of LaSiP3 and two polymorphs of CeSiP3. In situ X-ray diffraction studies revealed that the developed method bypasses formation of the thermodynamic dead-end, the binary SiP. Careful re-determination of the crystal structure ruled out the previously reported ordered centrosymmetric structure of CeSiP3 and showed that the main LnSiP3 polymorphs crystallize in the non-centrosymmetric Pna21 and Aea2 space groups featuring distinct distortions of the regular P square net to yield either cis-trans 1D phosphorus chains (Pna21) or disordered-2D phosphorus layers (Aea2). The disordered 2D nature of the P layers in the Aea2 LaSiP3 polymorph was confirmed by Raman spectroscopy. A unique centrosymmetric P21/c polymorph was observed for LaSiP3 and has a completely different crystal structure lacking P layers. Consecutive polymorphic transformations at increasing temperatures for LaSiP3(Pna21 → P21/c → Aea2) were derived from optimized synthetic profiles and confirmed by a combination of phonon computations and experimental in situ and ex situ annealings. Crystal structures of the LaSiP3 polymorphs were verified via advanced solid state NMR analysis using 31P MAS and 31P{139La} double resonance techniques. A combination of phonon and electronic structure calculations, NMR T1 relaxation times, UV/Vis/NIR spectroscopy, and resistivity measurements revealed that all the reported polymorphs are semiconductors with resistivities and thermal conductivities strongly dependent on the degree of distortion of P square layers in the crystal structure. Reported here, non-centrosymmetric LnSiP3 polymorphs with tunable resistivity and thermal conductivity provide a platform for the development of novel functional materials with a wide range of applications.

Natural selection and veridical perceptions.

Does natural selection favor veridical perceptions, those that more accurately depict the objective environment? Students of perception often claim that it does. But this claim, though influential, has not been adequately tested. Here we formalize the claim and a few alternatives. To test them, we introduce "interface games," a class of evolutionary games in which perceptual strategies compete. We explore, in closed-form solutions and Monte Carlo simulations, some simpler games that assume frequency-dependent selection and complete mixing in infinite populations. We find that veridical perceptions can be driven to extinction by non-veridical strategies that are tuned to utility rather than objective reality. This suggests that natural selection need not favor veridical perceptions, and that the effects of selection on sensory perception deserve further study.

Synthesis and Characterization of K and Eu Binary Phosphides.

The synthesis, structural characterization, and optical properties of the binary Zintl phases of α-EuP3, ß-EuP3, EuP2, and α-K4P6 are reported in this study. These crystal structures demonstrate the versatility of P fragments with dimensionality varying from 0D (P6 rings in α-K4P6) to 1D chains (EuP2) to 2D layers (both EuP3). EuP2 is isostructural to previously reported SrP2 and BaP2 compounds. The thermal stabilities of the EuP2 and both EuP3 phases were determined using differential scanning calorimetry (DSC), with melting temperatures of 1086 K for the diphosphide and 1143 K for the triphosphides. Diffuse reflectance spectroscopy indicated that EuP2 is an indirect semiconductor with a direct bandgap of 1.12(5) eV and a smaller indirect one, less than 1 eV. Both EuP3 compounds had bandgaps smaller than 1 eV.

Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-αßR-/- Mice.

Maternal infection with Zika virus (ZIKV) can lead to microcephaly and other congenital abnormalities of the fetus. Although ZIKV vaccines that prevent or reduce viremia in non-pregnant mice have been described, a maternal vaccine that provides complete fetal protection would be desirable. Here, we show that adenovirus (Ad) vector-based ZIKV vaccines induce potent neutralizing antibodies that confer robust maternal and fetal protection against ZIKV challenge in pregnant, highly susceptible IFN-αßR-/- mice. Moreover, passive transfer of maternal antibodies from vaccinated dams protected pups against post-natal ZIKV challenge. These data suggest that Ad-based ZIKV vaccines may be able to provide protection in pregnant females against fetal ZIKV transmission in utero as well as in infants against ZIKV infection after birth.

Analysis of the psychosocial impact of caretaking on the parents of an infant with severe congenital heart defect.

This case report considers the psychosocial burden of caring for an infant with a severe congenital heart defect (CHD) on parents. Improved prenatal diagnostics and postnatal surgical intervention have created a new and increasing demographic of children and adults with CHDs that require lifelong medical care. For this reason, primary caregivers spend excessive amounts of time in hospitals and medical facilities, and must regularly decipher vast amounts of unfamiliar medical terminology and concepts with varying levels of assistance from medical personnel. This often leads to marked psychological morbidities in parental caregivers, such as stress, anxiety and depression. The financial cost of caring for infants with CHD, including loss of employment opportunities, is another important factor that impacts the quality of life of caregivers. Frequent and extended travel to seek specialised medical care, often at distant medical centres, represents an additional burden.