Xylazine-Induced Necrotic Skin Ulcers in a Fentanyl-Injecting Individual in South Florida, United States: A Case Report.

Xylazine, commonly referred to as "Tranq," is an alpha-2-adrenergic receptor agonist that is FDA-approved only as a sedative and tranquilizer for veterinary use. However, its use as an adulterant in various illicit drugs, including fentanyl, has been on the rise, leading to its street name, "Tranq-Dope." Intravenous injection use of xylazine produces distinctive skin ulceration with accompanying necrosis, which can be considered virtually pathognomonic. A 41-year-old male with polysubstance abuse disorder presented to the emergency department with severe skin ulcerations on the right forearm and left calf with associated pain and erythema at injection sites. The concern for complicated skin tissue infection was acknowledged and the patient was admitted. The initial urine toxicology report was positive for cocaine, cannabinoids, benzodiazepines, and fentanyl. Upon detailed history-taking, the patient attested to recent changes in the sedative and euphoric effects of fentanyl use, which increased the index of suspicion for xylazine exposure. Immunoassay-based xylazine test strips were positive. Initially, he was administered broad-spectrum intravenous antibiotics, then switched to oral antibiotics at discharge. He was compliant with starting buprenorphine and buprenorphine-naloxone following discharge for management of his severe opioid use disorder. Xylazine's alpha-2-adrenergic agonistic properties in the periphery are thought to initiate a cascade of effects starting with vasoconstriction causing impaired blood perfusion hindering wound healing and increasing vulnerability to secondary infections. This case report aims to alert the medical community about the alarming occurrence of xylazine as an adulterant in illicit drugs and to describe the characteristic skin lesions associated with xylazine injections. Awareness of xylazine use should be considered in patients who develop necrotic skin ulcerations at injection sites along with alterations in typical effects of drug use.

Prolonged Itraconazole Therapy as Sole Treatment for Patients with Allergic Fungal Rhinosinusitis.

BACKGROUND: Currently, the mainstay of treatment for allergic fungal rhinosinusitis (AFRS) is surgical debridement along with topical or systemic steroids. However, prolonged systemic steroid therapy comes with side effects and is also sometimes contraindicated. Systemic antifungals have been used earlier as an adjunct to steroids or in refractory cases, but they have not been used as the sole primary treatment. OBJECTIVE: To study the effectiveness of sole Itraconazole therapy in patients with AFRS by comparison of clinical, radiological, and biochemical parameters before and after treatment. METHODS: Thirty-four patients diagnosed with localized sino-nasal AFRS were recruited and started on the tablet Itraconazole 200 mg orally twice daily for 3 months with q2weekly monitoring of liver function tests. The baseline clinical, radiological, and biochemical parameters were then compared with those after completion of 3 months of Itraconazole therapy. RESULTS: There was significant difference between all the parameters-clinical: SNOT-22 score (p < 0.001) and Meltzer endoscopy score (p < 0.001), radiological: Lund-Mackay score (p = 0.004) and 20-point CT score (p = 0.002), and biochemical: serum total IgE (p < 0.001), Aspergillus-specific IgE (p < 0.001), and absolute eosinophil count (p < 0.001). The clearance of the disease was more in anterior sinuses than the posterior ones. CONCLUSION: Prolonged Itraconazole can be given as sole therapy in AFRS, especially in patients for whom steroids are contraindicated or in those who are awaiting surgery. It can result in symptomatic and radiological improvement, but surgery still remains the definitive treatment option for AFRS for complete clearance of disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:545-551, 2024.

Can Superoxide Anions Predict the Malignant Potential of Carotid body Tumor? - A Pilot Study.

Currently, there is no consensus on estimating the malignant potential of Carotid Body Tumor (CBT) and the only way to predict a metastatic CBT is through DOTANOC Positron Emission Tomography (PET) scan. There is a well-established correlation between CBT and superoxide anions inside tumor cells. The purpose of this pilot study was to measure superoxide anions inside CBT cells and find if these can be used as marker to predict malignant potential of CBT. The results were also co-related with findings of DOTANOC PET scan retrospectively. The CBT tissue from 10 patients was stained using a fluorogenic dye and superoxide anions were measured by analysis of fluorescent image. The patients were divided into two groups - First group with four patients having potentially malignant CBT based upon clinico-surgical characteristics and second group with the rest of the six patients. It was seen that the superoxide anions were highest in the first group which included patients with metastatic carotid body tumor, patients with multiple paragangliomas and patient with positive family history (p = 0.011). The same patients also had metastasis and multiple tumors detected on DOTANOC PET scan. It was concluded that measuring superoxide anions in excised tumor tissue can be used to estimate malignant potential of CBT and can identify patients who truly require DOTANOC PET scan; without affecting the treatment, as it is an expensive investigation involving ionizing radiation and may not be available in all centres. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03623-6.

Comparison of lichen sclerosus in boys and girls: A systematic literature review of epidemiology, symptoms, genetic background, risk factors, treatment, and prognosis.

BACKGROUND: Studies concerning pediatric lichen sclerosus are limited, and, to date, there have been no studies comparing the course of lichen sclerosus in boys and girls. We sought to examine all publications on boys and girls with lichen sclerosus and assess and compare epidemiology, symptoms and signs, genetic background, risk factors, treatment, and prognosis. METHODS: A systematic search was performed in the Embase, Medline, Cochrane, and Web of Science databases. Inclusion criteria were information on children ages 0-18 years and a clinical or histologic diagnosis of lichen sclerosus. Literature from 1985 to 2021 was reviewed. RESULTS: A total of 1780 articles were retrieved from the search, of which 90 articles were eligible for inclusion. Boys and girls present similarly on many aspects; nonetheless, treatment and follow-up are approached differently. CONCLUSIONS: Though the clinical approach is often different, lichen sclerosus in boys and girls demonstrates many similarities. More research is needed, especially on follow-up, to gain a better understanding of the course of lichen sclerosus and establish an advanced management plan for children.

Indications and advantages of endoscopic trans-sphenoid approach for petrous apex lesions: two case reports.

BACKGROUND: The choice of surgical approach for a petrous apex lesion depends on its relationship with the internal carotid artery, degree of medial expansion and pathology. The correct identification of patients who will benefit from this approach is necessary. CASE REPORTS: Two adult patients presented with a lesion in the left petrous apex. Computed tomography showed a homogeneous mass extending anteromedially, and abutting the internal carotid artery and the sphenoid sinus in both patients. Using magnetic resonance imaging, a third recurrence of cholesterol granuloma in case one and cholesteatoma in case two were diagnosed. Both patients underwent trans-sphenoid excision, as the sphenoid sinus was well pneumatised and the lesion was medial to the internal carotid artery. CONCLUSION: Nasal endoscopic access to the petrous apex via the trans-sphenoid corridor should be preferred for benign lesions extending anteromedially in cases where lateral access is impeded by the internal carotid artery, the labyrinth and the facial nerve, and anterior trans-sphenoidal access offers a low-morbidity alternative.

Process Intensification of Enzymatic Synthesis of Flavor Esters: A Review.

The conventional flavor synthesis method suffers from low yields, time inefficiency, and extreme reaction conditions. Therefore, there is a necessity for the green and novel synthesis approach to overcome these limitations. The current review presents a holistic insight into different aspects associated with the synthesis of flavor esters using the immobilized enzyme. The application of process intensification tools such as ultrasound and microwave irradiation can enhance the reaction efficiency because of higher product recovery, less formation of by-products, and decreased energy consumption. This review presents the process intensification of value-added flavor esters synthesis and the mechanism of ultrasound and microwave action on the enzyme to enhance the enzyme activity and increase the reaction rate. It also summarizes the role of process intensification in enzymatic flavor ester synthesis, followed by specific examples as reported in the literature.

Male circumcision and Sexually transmitted Infections - An update.

Role of male circumcision (MC) as a tool to prevent sexually transmitted infections (STIs)/human immunodeficiency virus (HIV) was assessed. An attempt was made to search articles related to association between MC and STIs/HIV. A thorough search was carried out to find out quality articles published in indexed specialty journals. Centers for Disease Control and Prevention and World Health Organization (WHO) sites were also referred. Warm and moist environment of area under foreskin facilitates some pathogens to persist and replicate. Further, the thinness of foreskin predisposes it to minor trauma and abrasions that facilitate the entry of pathogens. MC reduces HIV infection risk by 50%-60% over time and reduces the risk of men acquiring herpes simplex virus-2 and human papillomavirus (HPV) that can cause penile and other anogenital cancers, by 30%. There is no significant reduction in risk of acquiring syphilis, but reduced risk of acquisition of Haemophilus ducreyi is reported. MC is reported to be beneficial in conditions such as traumatic injury, Balanitis Xerotica Obliterans, refractory balanoposthitis, and chronic, recurrent urinary tract infections. MC also reduces the chances of penile carcinoma by facilitating improved penile hygiene, lowering HPV/HIV transmission rates, and reducing chronic inflammatory conditions such as phimosis and balanitis. MC has been recommended by the WHO and UNAIDS in 2007 as an additional HIV prevention intervention in settings of high HIV prevalence. MC is an important adjunct to safe sex education, condom use, and vaccination (HPV) in reducing the global burden of HIV/STIs-related morbidity and mortality.

Adapting and Extending a Typology to Identify Vaccine Misinformation on Twitter.

Objectives. To adapt and extend an existing typology of vaccine misinformation to classify the major topics of discussion across the total vaccine discourse on Twitter.Methods. Using 1.8 million vaccine-relevant tweets compiled from 2014 to 2017, we adapted an existing typology to Twitter data, first in a manual content analysis and then using latent Dirichlet allocation (LDA) topic modeling to extract 100 topics from the data set.Results. Manual annotation identified 22% of the data set as antivaccine, of which safety concerns and conspiracies were the most common themes. Seventeen percent of content was identified as provaccine, with roughly equal proportions of vaccine promotion, criticizing antivaccine beliefs, and vaccine safety and effectiveness. Of the 100 LDA topics, 48 contained provaccine sentiment and 28 contained antivaccine sentiment, with 9 containing both.Conclusions. Our updated typology successfully combines manual annotation with machine-learning methods to estimate the distribution of vaccine arguments, with greater detail on the most distinctive topics of discussion. With this information, communication efforts can be developed to better promote vaccines and avoid amplifying antivaccine rhetoric on Twitter.

Exploring of greater yam (Dioscorea alata L.) genotypes through biochemical screening for better cultivation in south Gujarat zone of India.

Fifteen different genotypes of greater yam (Dioscorea alata) NGY-1, NGY-2, NGY-3, NGY-4, NGY-5, NGY-6, NGY-7, NGY-8, NGY-9, NGY-10, NGY-11, NGY-12, NGY-13, NGY-14 and Da-199 were procured from different places of south Gujarat, like Valsad, Navsari, Surat and Anand. Among the biochemical parameters total carbohydrate ranged between 51.87 and 87.85% from different genotypes, starch ranged from 47 to 80.67%, crude fat ranged from 0.6 to 2.32%, crude fibre ranged between 1.10 and 4.09%, anthocyanin content of genotypes ranged from 1.01 to 3.25 mg/g, beta-carotene content ranged between 0.97 and 1.88 µg/g. The antinutrients namely Diosgenin and Tannin ranged from 0.28 to 0.93% and 0.923 mg/100 g to 2.447 mg/100 g, respectively. RAPD analysis was also done by the help of 18 RAPD markers: OPA1, OPA2, OPA3, OPA13, OPB1, OPB6, OPB7, OPM1, OPM2, OPM4, OPM7, OPM11, OPM12, OPM13, OPM15, OPM16, OPM17 and OPM19 from which an average of 9.7 loci were detected with an average of 4.72 polymorphic loci which is 48.65% polymorphism per loci and 48.70% average polymorphism. From the overall study, it can be conferred that the study revealed highest carbohydrate content in NGY-3 (87.85%), fat (2.32%) and crude fiber content (4.09%) in NGY-11, ß-carotene in NGY-7 (1.88 µg/g), anthocyanin in NGY-4(3.25 mg/g). Lowest tannin (0.923 mg/100 g) and diosgenin (0.28%) was found in NGY-6, and NGY-7 respectively. For each of the biochemical parameters, the varieties with the optimum values may be cultivated. As the molecular studies revealed NGY-2 and NGY-3 have 96% similarities, they may be the duplicate of the same genotypes which can be studied further for better germplasm conservation.

Inhibition in the somatosensory system: An integrative neuropharmacological and neuroimaging approach.

The presented study investigates the functional role of GABA in somatosensory processing, using a combined neuropharmacological-neuroimaging approach. Three different GABA agonists (GABAA: alprazolam, ethanol; GABAB: baclofen) were investigated in a double blind cross-over design in 16 male participants, accomplishing a tactile perception task. Somatosensory evoked magnetic fields modulated by GABAR-agonists and placebo were recorded using whole-head magnetoencephalography. Peak latencies and amplitudes of primary (SI) and secondary (SII) somatosensory cortex source activities confirmed the previously reported role of GABA as a modulator of somatosensory processing. Significant inhibitory effects on the latency of SII and on the amplitude of SI and SII were found exclusively for alprazolam, a positive allosteric modulator at GABAA receptors. The GABAB agonist baclofen did not have any modulatory effect. Moreover, we investigated whether the observed effects of alprazolam on the level of SII were explainable by the mere propagation of activity from SI to SII modulated by GABAA receptors, independently from any further GABAA-mediated inhibition in SII. By estimating the transfer function between SI and SII activation under placebo conditions, we were able to predict SII activity for the administration of GABA receptors agonists under the assumption that GABA exclusively acts at the level of SI. By comparing measured and predicted data, we propose a model in which the initial activation of SI is modulated through GABAA receptors and subsequently propagated to SII, without any significant further inhibition. In addition, initial GABAA effects in SI appear to be strongly potentiated with time, selectively in SI but not in SII.

Verrucous lesions over external genitalia as a presenting feature of pemphigus vegetans.

Pemhigus vegetans is a rare variant of pemphigus vulgaris which primarily occurs in the flexures of the body. We report a case of pemphigus vegetans in an 85-year-old female presenting with hypertrophic verrucous lesions over external genitalia and perianal region. There was no history of preceding oral lesions. The diagnosis of pemphigus vegetans was considered on the clinical ground and confirmed by histopathological examination.

Acoustic cavitation promoted lipase catalysed synthesis of isobutyl propionate in solvent free system: Optimization and kinetic studies.

The present work highlights the effect of ultrasound on enzymatic synthesis of isobutyl propionate, a rum flavor by esterification of isobutanol and propionic acid in non-aqueous, solvent free system (SFS) using Fermase CALB™10000. The optimization study for different variables in presence of ultrasound showed a maximum conversion of 95.14% at 60°C temperature, 4% w/w enzyme dose, 1:3 acid:alcohol ratio, 40W power, 25kHz frequency, 50% duty cycle and 150rpm speed in 3h as compared to 10h of conventional method. The optimal enzyme loading was reduced to 4% w/w using ultrasound irradiation compared to 5% w/w of conventional. The efficiency of enzyme improved notably and can be reused up to seven cycles preserving its former activity. The application of ultrasound greatly enhanced esterification reactions by maintaining enzyme stability and improving the production yield. Moreover, owing towards a green approach, the synthesis is carried out in SFS for development of lucrative flavor ester. Bisubstrate kinetic models like random bi-bi, ping pong bi-bi and ordered bi-bi were applied to the experimental data using non-linear regression analysis. The experimental data and kinetic study revealed that reaction obeyed Ping-Pong bi-bi model with kinetic parameters, Vmax=50.0M/min/gcatalyst, KA=4.87×10-2M, KB=9.06×10-4M, KiA=9.8×10-1M, KiB=1.05×10-3M &SSE=2.74×10-4 for lipase catalysed synthesis of isobutyl propionate under ultrasound with inhibition by both acid and alcohol.

Renal Transplant Acute Rejection with Lower Mycophenolate Mofetil Dosing and Proton Pump Inhibitors or Histamine-2 Receptor Antagonists.

BACKGROUND: Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil (MMF) and proton pump inhibitors (PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF-PPI versus patients taking MMF-ranitidine. OBJECTIVE: The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2RA). METHODS: This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation. RESULTS: Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2RA. There was no significant difference in acute rejection within 1 year (H2RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression (MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups. CONCLUSION: Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2RA were not at increased risk of acute rejection within 1 year posttransplantation.

Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome.

Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.

Loss of heat shock protein 70 from apical region of buffalo (Bubalus bubalis) sperm head after freezing and thawing.

The post-thaw fertility of frozen-thawed mammalian spermatozoa is substantially low as compared with that of fresh sperm. Furthermore, the post-thaw fertility of the cryopreserved buffalo sperm has been reported to be poor as compared with that of cattle sperm. Recently, heat shock protein 70 (HSP70) has been found to play a critical role in mammalian fertilization and early embryonic development in boar and cattle. However, the presence of such fertility-related HSP70 in buffalo sperm and its status after cryopreservation has not been reported so far. Thus, a study was conducted to determine the effect of cryopreservation on the level and distribution pattern of HSP70 molecule in buffalo sperm after cryopreservation. Buffalo semen samples, after dilution in semen extender, were aliquoted in straws and divided into two groups. One group was not cryopreserved, and the other group was cryopreserved for 60 days. Sperm proteins were extracted from both non-cryopreserved (NC) and cryopreserved (C) sperm and subjected to Western blot analysis for detection of HSP70 using a monoclonal anti-HSP70 antibody. The distribution pattern of these proteins in buffalo sperm was also monitored before and after cryopreservation using indirect immunofluorescence technique. A prominent 70-kDa protein band of HSP70 protein was detected in protein extracts of both NC and C buffalo sperm. Densitometry analysis revealed that the intensity of 70-kDa HSP70 protein band of cryopreserved sperm decreased significantly (P < 0.05) compared with that of NC sperm. However, the level of HSP70 in cryopreserved extended seminal plasma (ESP) did not change as compared with that of NC samples indicating a possible degradation of HSP70 in the spermatozoa itself rather than leakage of the protein into the ESP. Furthermore, Western blot also confirmed that several HSP70 immunoreactive protein bands detected in the ESP were contributed by the egg yolk that was added to the extender. Immunocytochemistry revealed that HSP70 proteins were distributed over the apical region of sperm head and/or acrosome, post-acrosomal, and middle piece regions of NC buffalo spermatozoa. However, the fluorescence signal of apical region of sperm head was lost significantly (P < 0.05) after a cycle of freezing and thawing. Thus, the present study confirmed that there was loss of HSP70 from buffalo sperm head after freezing and thawing of buffalo spermatozoa, and this may be one of the causes of the reduced post-thaw fertility of sperm in this species.

"Nil per oral after midnight": Is it necessary for clear fluids?

Fasting before general anaesthesia aims to reduce the volume and acidity of stomach contents, thus reducing the risk of regurgitation and aspiration. Recent guidelines have recommended a shift in fasting policies from the standard 'nil per oral from midnight' to a more relaxed policy of clear fluid intake a few hours before surgery. The effect of preoperative oral administration of 150 ml of water 2 h prior to surgery was studied prospectively in 100 ASA I and II patients, for elective surgery. Patients were randomly assigned to two groups. Group I (n = 50) was fasting overnight while Group II (n = 50) was given 150 ml of water 2 h prior to surgery. A nasogastric tube was inserted after intubation and gastric aspirate was collected for volume and pH. The gastric fluid volume was found to be lesser in Group II (5.5 ± 3.70 ml) than Group I (17.1 ± 8.2 ml) which was statistically significant. The mean pH values for both groups were similar. Hence, we conclude that patients not at risk for aspiration can be allowed to ingest 150 ml water 2 h prior to surgery.

Seasonal variation and circadian rhythmicity of the prolactin profile during the summer months in repeat-breeding Murrah buffalo heifers.

The present study was undertaken to determine a detailed endocrine profile for prolactin and progesterone during the oestrous cycle in repeat-breeding Murrah buffalo heifers during summer and winter. Hormone concentrations were quantified in blood plasma samples collected over the oestrous cycle in both winter and summer, as well as in samples collected during the summer months to observe circadian rhythmicity. The mean plasma prolactin concentration during the winter months ranged from 3.10 +/- 0.48 to 9.17 +/- 1.39 ng mL(-1); during the summer months, plasma prolactin concentrations ranged from 248.50 +/- 16.03 to 369.63 +/- 25.13 ng mL(-1). During the winter months, the mean plasma progesterone concentration ranged from 0.20 +/- 0.00 to 3.04 +/- 0.34 ng mL(-1), which was significantly higher (P < 0.01) than the prolactin concentrations recorded in the summer months (range 0.20 +/- 0.00 to 1.48 +/- 0.13 ng mL(-1)). Plasma prolactin and progesterone concentrations were negatively correlated (r = -0.24) during the summer oestrous cycle, which indicates prolactin-induced suppression of progesterone secretion through poor luteal development. During the summer, a circadian rhythmicity was observed in buffaloes and the results indicate that high prolactin secretion contributes to poor fertility by lowering gonadal hormone (progesterone) secretion. It was concluded from the present study that prolactin and progesterone profiles during the summer and winter months are directly correlated with the reproductive performance of buffaloes. The finding also validates the hypothesis that hyperprolactinaemia may cause acyclicity/infertility in buffaloes during the summer months due to severe heat stress.