Botox in below knee amputation for the management of post-operative contracture: a systematic review.

During the 1970s, scientists first used botulinum toxin to treat strabismus. While testing on monkeys, they noticed that the toxin could also reduce wrinkles in the glabella area. This led to its widespread use in both medical and cosmetic fields. The objective of the study was to evaluate the potential use of Botox in managing post-operative contracture after below-knee amputation. We conducted a systematic review In Pubmed, Cochrane Library, Embase, and Google Scholar using the MESH terms Botox, botulinum toxin, post-operative contracture, amputation, and below knee amputation. Our goal was to evaluate the potential use of Botox to manage post-operative contracture in patients who have undergone below-knee amputation. Our findings show evidence in the literature that Botox can effectively manage stump hyperhidrosis, phantom pain, and jumping stump, but no clinical trial has been found that discusses the use of Botox for post-operative contracture. Botox has been used in different ways to manage spasticity. Further studies and clinical trials are needed to support the use of Botox to manage this complication.

Ammonium perchlorate: serum dosimetry, neurotoxicity, and resilience of the neonatal rat thyroid system.

The environmental contaminant perchlorate impairs the synthesis of thyroid hormones by reducing iodine uptake into the thyroid gland. Despite this known action, moderate doses of perchlorate do not significantly alter serum thyroid hormone in rat pups born to exposed dams. We examined perchlorate dosimetry and responsivity of the thyroid gland and brain in offspring following maternal exposure to perchlorate. Pregnant rat dams were delivered perchlorate in drinking water (0, 30, 100, 300, 1000 ppm) from gestational day 6 to postnatal day (PN) 21. Perchlorate was present in the placenta, milk, and serum, the latter declining in pups over the course of lactation. Serum and brain thyroid hormone were reduced in pups at birth but recovered to control levels by PN2. Dramatic upregulation of Nis was observed in the thyroid gland of the exposed pup. Despite the return of serum thyroid hormone to control levels by PN2, expression of several TH-responsive genes was altered in the PN14 pup brain. Contextual fear learning was unimpaired in the adults, supporting previous reports. Declining levels of serum perchlorate and a profound upregulation of Nis gene expression in the thyroid gland are consistent with the rapid return to the euthyroid state in the neonate. However, despite this recovery, thyroid hormone insufficiencies in serum and brain beginning in utero and present at birth appear sufficient to alter TH action in the fetus and subsequent trajectory of brain development. Biomarkers of that altered trajectory remain in the brain of the neonate, demonstrating that perchlorate is not devoid of effects on the developing brain.

Bacterial Species Causing Secondary Pneumonia Infection in Pregnant Women with COVID-19.

Sputum samples were taken from pregnant women infected with the COVID-19, where the study was conducted on 112 cases, and the results showed that 87 cases developed secondary bacterial infections at a rate of 78% and 25 cases were negative by 22%. The samples were cultured on solid media and incubated at 37°C. Then the samples were diagnosed by biochemical tests and using the API system. Six species of bcteria have been isolated (S. aureus, K.pneumonia P. auroginosa, H. influenza, S. pneumonia S. pyogens) by 31, 29, 12, 10, 7, and 5 isolates, respectively, where the result showed that the most common types of pneumonia were S. aureus with a percentage of 34%, followed by K. pneumonia with a percentage of 29%. The sensitivity of the isolates to eight types of common antibiotics was tested (Erythromycin, Trimethoprim, Ampicillin, Tetracycline, Augmentin, Nitrofurantoin, Meropenem, and Amikacin), where the isolates showed a high resistance to antibiotics (Erythromycin, Trimethoprim, Ampicillin), a high sensitivity of 100% to the Nitrofurantoin, and an average sensitivity to other antibiotics.

Two Cases of Venous Thromboembolism Shortly After Adenovirus-Based COVID-19 Vaccination.

As the coronavirus disease 2019 (COVID-19) global pandemic continues, multiple vaccines have been developed to decrease infection rate and number of deaths. Vaccine administration is especially important as new COVID-19 variants emerge. While the number of severe thromboembolic events reported after adenovirus-based vaccination has gained attention, there is little information regarding the presentation and management of post-vaccination venous thromboembolism (VTE). Here, we present two cases of VTE after the Janssen vaccine administration. In the first case, a 98-year-old African American female with hypertension developed bilateral lower extremity edema that evolved into unilateral lower extremity edema 20-35 days following the Janssen vaccine administration. She was found to have an extensive unilateral proximal femoral deep vein thrombosis (DVT) 35 days after the vaccination. In the second case, a 64-year-old African American female developed ecchymosis and unilateral edema six days after the Janssen vaccine administration. She was found to have proximal superficial vein thrombosis two days later. In both cases, laboratory data, including platelets and anti-heparin antibodies were within normal limits. Thus, VTE may be an adverse effect of the Janssen vaccine or any adenovirus-based vaccine, but further surveillance and investigation to elucidate this association are necessary. We advise practitioners to have a high index of suspicion for thrombosis after Janssen vaccine administration, regardless of the presence of thrombocytopenia, and avoidance of heparin products until heparin antibody results return.

Consensus on Social Determinants of Health Knowledge Topics and Behavior Learning Goals Across Primary Care Residencies: Results of a Delphi Study.

PURPOSE: Social determinants of health (SDH) are a substantial contributor to health outcomes and health inequities across populations. The Accreditation Council for Graduate Medical Education has called for the incorporation of SDH into graduate medical education (GME), yet there is no consensus on what SDH knowledge or skills residents in primary care specialties should have on completion of training. The aim of this study was to develop expert consensus on the most important SDH knowledge topics and behavior learning goals for residents in 4 primary care fields. METHOD: The authors used a modified Delphi technique to develop consensus among experts in internal medicine, pediatrics, family medicine, and obstetrics and gynecology across the United States via a survey administered between February and October 2021. They conducted a literature review on SDH in GME to develop an initial set of topics and learning goals and recruited experts who published about SDH and GME or led an SDH curriculum in GME. Consensus was determined a priori as 80% agreement that a topic or learning goal was very or extremely important. RESULTS: Forty-one experts participated in the first round of the survey and 33 participated in the second round (80% retention). Experts reached consensus on the importance of 22/51 (43%) topics and 18/47 (38%) learning goals. Topics reaching consensus emphasized structural forces, broad domains of SDH, resources for addressing SDH, and advocacy strategies and resources. Learning goals reaching consensus focused on individual- and interpersonal-level behaviors. CONCLUSIONS: To the authors' knowledge, this study represents the first rigorous evaluation of expert consensus on SDH in GME across 4 primary care specialties. The results could inform curriculum development and implementation and program evaluation, residency program goals, and shared GME milestones. Among other things, future studies can assess expert consensus on SDH in GME across nonprimary care specialties.

The Effect of Microcosm Biofilm Decontamination on Surface Topography, Chemistry, and Biocompatibility Dynamics of Implant Titanium Surfaces.

Since the inception of dental implants, a steadily increasing prevalence of peri-implantitis has been documented. Irrespective of the treatment protocol applied for the management of peri-implantitis, this biofilm-associated pathology, continues to be a clinical challenge yielding unpredictable and variable levels of resolution, and in some cases resulting in implant loss. This paper investigated the effect of microcosm biofilm in vitro decontamination on surface topography, wettability, chemistry, and biocompatibility, following decontamination protocols applied to previously infected implant titanium (Ti) surfaces, both micro-rough -Sandblasted, Large-grit, Acid-etched (SLA)-and smooth surfaces -Machined (M). Microcosm biofilms were grown on SLA and M Ti discs. These were treated with TiBrushes (TiB), combination of TiB and photodynamic therapy (PDT), combination of TiB and 0.2%CHX/1%NaClO, plus or minus Ultraviolet-C (UV-C) radiation. Surface topography was evaluated by Scanning Electron Microscopy (SEM) and Laser Surface Profilometry. Surface function was analysed through wettability analysis. Surface chemistry evaluation of the discs was performed under SEM/Energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). Biocompatibility was tested with the cytocompatibility assay using human osteoblast-like osteosarcoma cell line (MG-63) cells. Elemental analysis of the discs disclosed chemical surface alterations resulting from the different treatment modalities. Titanium, carbon, oxygen, sodium, aluminium, silver, were identified by EDX as the main components of all the discs. Based on the data drawn from this study, we have shown that following the decontamination of Ti surfaces the biomaterial surface chemistry and topography was altered. The type of treatment and Ti surface had a significant effect on cytocompatibility (p = 0.0001). Although, no treatment modality hindered the titanium surface biocompatibility, parameters such as the use of chemical agents and micro-rough surfaces had a higher cytotoxic effect in MG-63 cells. The use of smooth surfaces, and photofunctionalisation of the TiO2 layer had a beneficial effect on cytocompatibility following decontamination.

The Structural Analysis: Incorporating Structurally Competent Clinical Reasoning into Case-Based Presentations.

Structural and social determinants of health account for the health disparities we see along social hierarchies, and their impact has been made more evident by the recent COVID-19 pandemic. There have been increasing calls to incorporate structural competency into medical education. The structural and social context, however, has yet to be fully integrated into everyday clinical practice and little has been published on how to concretely imbed structural competency into clinical reasoning. The authors provide a framework for structural analysis, which incorporates four key steps: (1) developing a prioritized clinical problem list, (2) identifying social and structural root causes for clinical problems, (3) constructing and documenting a prioritized structural problem list, and (4) brainstorming solutions to address structural barriers and social needs. They show how structural analysis can be used to operationalize structural reasoning into everyday inpatient and outpatient clinical assessments.

Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain.

Iodine is essential for the production of thyroid hormones. Perchlorate is an environmental contaminant that interferes with iodine uptake into the thyroid gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for brain development, exposure to perchlorate during pregnancy is of concern for the developing fetal brain. In this study, we (1) define profiles of thyroid hormone in the maternal and fetal compartments of pregnant rats in response to inhibition of the sodium-iodide symporter (NIS) by perchlorate and (2) expand inquiry previously limited to serum to include fetal thyroid gland and brain. Perchlorate was added to the drinking water (0, 1, 30, 300, and 1000 ppm) of pregnant rat dams from gestational days (GD) 6-20. On GD20, blood, thyroid gland, and brain were collected from the fetus and dam for thyroid hormone and molecular analyses. Thyroid gland and serum thyroid hormones were dose-dependently reduced, with steeper declines evident in the fetus than in the dam. The thyroid gland revealed perturbations of thyroid hormone-action with greater sensitivity in the fetus than the dam. Thyroid hormones and thyroid hormone-responsive gene expression were reduced in the fetal cortex portending effects on brain development. These findings are the first quantitative assessments of perchlorate-induced deficits in the fetal thyroid gland and fetal brain. We provide a conceptual framework to develop a quantitative NIS adverse outcome pathway for serum thyroid hormone deficits and the potential to impact the fetal brain. Such a framework may also serve to facilitate the translation of in vitro bioactivity to the downstream in vivo consequences of NIS inhibition in the developing fetus.

Factors Associated with Long-Term Retention in Buprenorphine-Based Addiction Treatment Programs: a Systematic Review.

BACKGROUND: The average length of buprenorphine treatment for opioid use disorder is less than 6 months. OBJECTIVE: We conducted a systematic review to determine what factors were associated with longer retention in buprenorphine treatment. DESIGN: We searched Medline, Embase, and Cochrane Database of Systematic Reviews in February 2018. Articles were restricted to randomized controlled trials on human subjects, written in English, which contained ≥ 24 weeks of objective data on retention in buprenorphine treatment. MAIN MEASURES: We assessed whether dose of buprenorphine, treatment setting, or co-administration of behavioral therapy was associated with retention rates. KEY RESULTS: Over 14,000 articles were identified. Thirteen articles (describing 9 studies) met inclusion criteria. Measures of retention varied widely. Three studies compared doses of buprenorphine between 1 and 8 mg and showed significantly higher rates of retention with higher doses (p values < 0.01). All other studies utilized buprenorphine doses between 8 and 24 mg daily, without comparison. No study found a significant difference in retention between buprenorphine alone and buprenorphine plus behavioral therapy (p values > 0.05). Initiating buprenorphine while hospitalized or within criminal justice settings prior to outpatient treatment programs was significantly associated with retention in buprenorphine treatment (p values < 0.01 respectively). CONCLUSIONS: Setting of treatment initiation and a higher buprenorphine dose are associated with improved long-term treatment retention. More objective data on buprenorphine treatment programs are needed, including a standardized approach to defining retention in buprenorphine treatment programs. REGISTRATION: This review was registered with PROSPERO (#CRD42019120336) in March 2019.

Whole Genome Sequencing of SARS-CoV-2 Strains in COVID-19 Patients From Djibouti Shows Novel Mutations and Clades Replacing Over Time.

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.

Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate.

Many xenobiotics are identified as potential thyroid disruptors due to their action to reduce circulating levels of thyroid hormone, most notably thyroxine (T4). Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals yet correlating the impact of chemically induced changes in serum T4 to perturbed brain development remains elusive. A number of thyroid-specific neurodevelopmental assays have been proposed, based largely on the model thyroid hormone synthesis inhibitor propylthiouracil (PTU). This study examined whether thyroid disrupting chemicals acting distinct from synthesis inhibition would result in the same alterations in brain as expected with PTU. The perfluoroalkyl substance perfluorohexane sulfonate (50 mg/kg/day) and the antimicrobial Triclosan (300 mg/kg/day) were administered to pregnant rats from gestational day 6 to postnatal day (PN) 21, and a number of PTU-defined assays for neurotoxicity evaluated. Both chemicals reduced serum T4 but did not increase thyroid stimulating hormone. Both chemicals increased expression of hepatic metabolism genes, while thyroid hormone-responsive genes in the liver, thyroid gland, and brain were largely unchanged. Brain tissue T4 was reduced in newborns, but despite persistent T4 reductions in serum, had recovered in the PN6 pup brain. Neither treatment resulted in a low dose PTU-like phenotype in either brain morphology or neurobehavior, raising questions for the interpretation of serum biomarkers in regulatory toxicology. They further suggest that reliance on serum hormones as prescriptive of specific neurodevelopmental outcomes may be too simplistic and to understand thyroid-mediated neurotoxicity we must expand our thinking beyond that which follows thyroid hormone synthesis inhibition.

Mechanistic Computational Model for Extrapolating In Vitro Thyroid Peroxidase (TPO) Inhibition Data to Predict Serum Thyroid Hormone Levels in Rats.

High-throughput in vitro assays are developed to screen chemicals for their potential to inhibit thyroid hormones (THs) synthesis. Some of these experiments, such as the thyroid peroxidase (TPO) inhibition assay, are based on thyroid microsomal extracts. However, the regulation of thyroid disruption chemicals is based on THs in vivo serum levels. This necessitates the estimation of thyroid disruption chemicals in vivo tissue levels in the thyroid where THs synthesis inhibition by TPO takes place. The in vivo tissue levels of chemicals are controlled by pharmacokinetic determinants such as absorption, distribution, metabolism, and excretion, and can be described quantitatively in physiologically based pharmacokinetic (PBPK) models. An integrative computational model including chemical-specific PBPK and TH kinetics models provides a mechanistic quantitative approach to translate thyroidal high-throughput in vitro assays to in vivo measures of circulating THs serum levels. This computational framework is developed to quantitatively establish the linkage between applied dose, chemical thyroid tissue levels, thyroid TPO inhibition potential, and in vivo TH serum levels. Once this link is established quantitatively, the overall model is used to calibrate the TH kinetics parameters using experimental data for THs levels in thyroid tissue and serum for the 2 drugs, propylthiouracil and methimazole. The calibrated quantitative framework is then evaluated against literature data for the environmental chemical ethylenethiourea. The linkage of PBPK and TH kinetics models illustrates a computational framework that can be extrapolated to humans to screen chemicals based on their exposure levels and potential to disrupt serum THs levels in vivo.

Extrapolating In Vitro Screening Assay Data for Thyroperoxidase Inhibition to Predict Serum Thyroid Hormones in the Rat.

Thyroperoxidase (TPO) is an enzyme essential for thyroid hormone (TH) synthesis and a target site for a number of xenobiotics that disrupt TH homeostasis. An in vitro high-throughput screening assay for TPO inhibition, the Amplex UltraRed-TPO (AUR-TPO), has been used to screen the ToxCast chemical libraries for this action. Output from this assay would be most useful if it could be readily translated into an in vivo response, namely a reduction of TH in serum. To this end, the relationship between TPO inhibition in vitro and serum TH decreases was examined in rats exposed to 2 classic TPO inhibitors, propylthiouracil (PTU) and methimazole (MMI). Serum and gland PTU, MMI, and TH levels were quantified using tandem liquid chromatography mass spectrometry. Thyroperoxidase activity was determined in thyroid gland microsomes treated with PTU or MMI in vitro and ex vivo from thyroid gland microsomes prepared from exposed animals. A quantitative model was constructed by contrasting in vitro and ex vivo AUR-TPO results and the in vivo time-course and dose-response analysis. In vitro:ex vivo correlations of AUR-TPO outputs indicated that less than 30% inhibition of TPO in vitro was sufficient to reduce serum T4 by 20%, a degree of regulatory significance. Although further testing of model estimates using other TPO inhibitors is essential for verification of these initial findings, the results of this study provide a means to translate in vitro screening assay results into predictions of in vivo serum T4 changes to inform risk assessment.

The time is now: Fostering relationship-centered discussions about patients' social determinants of health.

OBJECTIVE: This paper discusses the importance of developing best practices in communication strategies to identify and act on social determinants of health (SDOH) in care settings in ways that minimizes shame and builds patient trust in the process. DISCUSSION: We leverage the relationship-centered care framework to provide health care teams guidance in how to foster meaningful discussions about SDOH at three pivotal points in the process: 1) at the initial screening; 2) once an unmet social need has been identified; and 3) when exchanging SDOH data with team members and external organizations. CONCLUSION: This discussion piece uses a relationship-centered framework to offer several evidence-based recommendations for health care systems on how to help their workforce respectfully listen and collaborate with patients to address SDOH. Additional research into patient and provider perceptions of relationship-centered communication surrounding screening and referral practices can help further adapt and refine best practices to maximize chances for addressing patients' SDOH.

Trichloroethylene exposure in mid-pregnancy decreased fetal weight and increased placental markers of oxidative stress in rats.

Although epidemiology studies have associated maternal trichloroethylene (TCE) exposure with decreased birth weight and preterm birth, mechanistic explanations for these associations are currently lacking. We hypothesized that TCE targets the placenta with adverse consequences for pregnancy outcomes. Pregnant Wistar rats were exposed orally to vehicle or 480 mg TCE/kg body weight from gestational days (gd) 6-16, and tissues were collected on gd 16. Exposure to TCE significantly decreased average fetal weight without reducing maternal weight. In placenta, TCE significantly increased 8-hydroxy-deoxyguanosine, global 5-hydroxymethylcytosine, and mRNA expression of Tet3, which codes for an enzyme involved in 5-hydroxymethylcytosine formation. Furthermore, glutathione S-transferase activity and immunohistochemical staining were increased in placentas of TCE-exposed rats. The present study provides the first evidence that TCE increases markers of oxidative stress in placenta in a fetal growth restriction rat model, providing new insight into the placenta as a potentially relevant target for TCE-induced adverse pregnancy outcomes.

Amelioration of the Protein Expression of Cox2, NFκB, and STAT-3 by Some Antioxidants in the Liver of Sodium Fluoride-Intoxicated Rats.

The present study aimed to explore the efficiency of N-acetyl cysteine (NACC) or thymoquinone (TMQ) alone or in combination in the downregulation of inflammatory molecule expression and decreasing hepatic injury in response to sodium fluoride (SF). Sodium fluoride upregulated serum alanine and aspartate transferases activities, tumor necrosis factor α and hepatic malondialdehyde and nitric oxide levels, and the expression of cyclooxygenase 2, nuclear factor κB cell, and signal transducer and activator of transcription 3. In contrast, hepatic glutathione level, superoxide dismutase activity, and nuclear factor erythroid 2-related factor 2 expression were decreased. However, the concurrent treatment with antioxidants, alone or in combination, modulated the levels of these parameters. Histopathological examination revealed that SF treatment resulted in focal areas of massive hepatic degeneration and many degenerated hepatocytes, whereas the treatment with TMQ or NACC exhibited moderate improvement in cellular degeneration of the liver with many abnormal cells. Rats receiving a combination of TMQ and NACC showed marked improvement in cellular degeneration of liver with apparently normal hepatic architecture with very few degenerated hepatocytes. The results also revealed that the combination of TMQ and NACC is the most effective regimen in ameliorating SF toxicity, suggesting their efficacy against the toxicity of fluoride compounds. Their activities might be mediated via multiple molecular pathways.

Liposomal Curcumin Attenuates the Incidence of Oxidative Stress, Inflammation, and DNA Damage Induced by Copper Sulfate in Rat Liver.

BACKGROUND: Copper is an essential element that is used widely in agriculture as fungicides and insecticides; for example, it is used to control schistosomiasis and as an antiseptic and germicide. Copper sulfate (CuSO4) induces multiorgan dysfunction through the stimulation of reactive oxygen species and oxidative stress. Despite the numerous pharmacological effects of curcumin (CUR), its pharmacokinetic properties are less promising. Hence, there is an urgent need for novel, effective strategies to attenuate heavy metal toxicity and consequently improve the treatment efficiency. Liposomal curcumin (L-CUR) improves the dissolution, stability, and bioavailability of treatment agents. This study compared the efficacy of CUR and L-CUR with that of desferrioxamine (DES), which is a heavy metal chelator against CuSO4 hepatotoxicity. METHODS: All treatments with the aforementioned antioxidants were administered for 7 days along with CuSO4. Serum levels of alanine aminotransferase, aspartate transaminase, lactate dehydrogenase, and C-reactive protein, hepatic nitric oxide (NO), and lipid peroxides (malondialdehyde) were measured; protein expression of cyclooxygenase 2 and DNA fragmentation were evaluated. Histopathological examinations were also conducted. RESULTS: A toxic dose of CuSO4 induced elevations in the previously measured parameters; these increases were reduced by the tested antioxidants, whereas glutathione (GSH) and superoxide dismutase (SOD) levels were decreased. Treatment with the antioxidants in question modulated these levels. Liposomal CUR has more hepatoprotective efficiency than CUR, and its efficacy was similar to that of DES. The histopathological examinations confirmed these results. CONCLUSIONS: Liposomal CUR may be useful for the prevention of CuSO4-induced liver injury. Cyclooxygenase 2 protein expression and DNA fragmentation were involved in CuSO4 toxicity and treatment.