Actinomycetes - The Repertoire of Diverse Bioactive Chemical Molecules: From Structures to Antibiotics.

The urgent need for novel antibiotics in the face of escalating global antimicrobial resistance necessitates innovative approaches to identify bioactive compounds. Actinomycetes, renowned for their prolific production of antimicrobial agents, stand as a cornerstone in this pursuit. Their diverse metabolites exhibit multifaceted bioactivities, including potent antituberculosis, anticancer, immunomodulatory, immuno-protective, antidiabetic, etc. Though terrestrial sources have been exploited significantly, contemporary developments in the field of antimicrobial drug discovery have put marine actinomycetes in a prominent light as a promising and relatively unexplored source of novel bioactive molecules. This is further boosted by post-genomic era advances like bioinformatics-based secretome analysis and reverse engineering that have totally revitalized actinomycetes antibiotic research. This review highlights actinomycetes-based chemically diverse scaffolds and clinically validated antibiotics along with the enduring significance of actinomycetes from untouched ecosystems, especially with recent advanced techniques in the quest for next-generation antimicrobials.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways.

During and after the COVID-19 pandemic,Tuberculosis (TB) has reestablished with higher figures due to interruptions in the Directly Observed Treatment Short course (DOTS) despite underreporting. The rising consequences would have extended to extra-pulmonary forms of TB as well, including Tuberculous Meningitis (TBM). Considering the fact that TBM is the most dangerous and worst form of TB, we found the need to scan the literature to highlight various aspects of TBM. Epidemiology of TBM is proportionally less frightening, but the consequent mortalities and morbidities are more alarming than pulmonary TB. Here, we address critical research gaps in Tuberculous Meningitis that warrant further investigations. The highlighted aspects encompass a comprehensive understanding of TBM's clinical presentation and improved diagnostic tools for timely detection, the exploration of innovative chemotherapies and surgical interventions, the unraveling of the role of the blood-brain barrier in disease onset, investigating of the contributions of various brain cells to TBM development, deciphering the complex inflammatory response, exploring the involvement of Matrix Metalloproteinases in tissue damage, delving into host-pathogen genetics influencing susceptibility, utilizing robust in-vivo and in-vitro models for mechanistic insights, and more importantly between TBM and SARS-COVID-19 are discussed. Addressing these gaps will substantially advance our understanding of TBM's complex pathogenesis, contributing to more effective diagnostic, therapeutic, and preventive strategies against this debilitating disease.

Exogenously applied nicotinic acid alleviates drought stress by enhancing morpho-physiological traits and antioxidant defense mechanisms in wheat.

Across the globe, the frequent occurrence of drought spells has significantly undermined the sustainability of modern high-input farming systems, particularly those focused on staple crops like wheat. To ameliorate the deleterious impacts of drought through a biologically viable and eco-friendly approach, a study was designed to explore the effect of nicotinic acid on different metabolic, and biochemical processes, growth and yield of wheat under optimal moisture and drought stress (DS). The current study was comprised of different levels of nicotinic acid applied as foliar spray (0 g L-1, 0.7368, 1.477, 2.2159 g L-1) and fertigation (0.4924, 0.9848, and 1.4773 g L-1) under normal conditions and imposed drought by withholding water at anthesis stage. The response variables were morphological traits such as roots and shoots characteristics, yield attributes, grain and biological yields along with biosynthesis of antioxidants. The results revealed that nicotinic acid dose of 2.2159 g L-1 out-performed rest of treatments under both normal and DS. The same treatment resulted in the maximum root growth (length, fresh and dry weights, surface area, diameter) and shoot traits (length, fresh and dry weights) growth. Additionally, foliar applied nicotinic acid (2.2159 g L-1) also produced as the highest spike length, grains spike-1, spikelet's spike-1 and weight of 1000 grains. Moreover, these better yield attributes led to significantly higher grain yield and biological productivity of wheat. Likewise in terms of physiological growth of wheat under DS, the same treatment remained superior by recording the highest SPAD value, relative water content, water potential of leaves, leaf area, stomatal conductance (292 mmolm-2S-1), internal carbon dioxide concentration, photosynthesis and transpiration rate. Interestingly, exogenously applied nicotinic acid remained effective in triggering the antioxidant system of wheat by recording significantly higher catalase, peroxidase, superoxide dismutase and ascorbate peroxidase.

Synthesis, Characterization, and Antimicrobial Activity of Ultra-Short Cationic ß-Peptides.

The development of new antibiotics is urgently required because of the rapidly growing resistance against conventional antibiotics. The antimicrobial peptides show potential as small antibiotic molecules. The stability of peptides is a primary concern for the use of peptides as drugs. Introducing ß-amino acids into peptide sequences can be useful in preventing biological degradation by proteolytic enzymes. Herein, we describe the synthesis, characterization, and antimicrobial activity of ultra-short cationic ß-peptides, LA-ß3,3-Pip-ß2,2-Ac6c-PEA, P1; LA-ß3,3-Pip(G)-ß2,2-Ac6c-PEA, P2; LAU-ß3,3-Pip-ß2,2-Ac6c-PEA, P3, and LAU-ß3,3-Pip(G)-ß2,2-Ac6c-PEA, P4. Peptides P1-P4 were evaluated against Gram-negative, Gram-positive, MRSA, and multi-drug resistant E. coli (MDR-E. coli). P3 exhibited the most potent antimicrobial activity against E. coli, S. epidermidis, S. aureus, K. pneumoniae, S. mutans, and E. faecalis, with MIC values 0.5, 2, 0.5, 1, 2, and 1 µg/mL, respectively. P3 exhibited time- and concentration-dependent bactericidal activities against E. coli, S. aureus, and E. faecalis with a killing rate of 1.6 logs/h. The treatment of E. coli with peptide P3 showed membrane disruption. In addition, P3 exhibited the inhibition of biofilm produced by E. coli, synergism with antibiotics (ciprofloxacin, streptomycin, and ampicillin), 100% cell viability against AML12, RAW 264.7, and HEK-293 cell lines at 1, and 10 µg/mL concentrations.

Dose optimization of silicon for boosting arbuscular mycorrhizal fungi colonization and cadmium stress mitigation in maize (Zea mays L.).

The foliar applied silicon (Si) has the potential to ameliorate heavy metals, especially cadmium (Cd) toxicity; however, Si dose optimization is strategically important for boosting the growth of soil microbes and Cd stress mitigation. Thus, the current research was performed to assess the Si-induced physiochemical and antioxidant trait alterations along with Vesicular Arbuscular Mycorrhiza (VAM) status in maize roots under Cd stress. The trial included foliar Si application at the rate of 0, 5, 10, 15, and 20 ppm while Cd stress (at the rate of 20 ppm) was induced after full germination of maize seed. The response variables included various physiochemical traits such as leaf pigments, protein, and sugar contents along with VAM alterations under induced Cd stress. The results revealed that exogenous application of Si in higher doses remained effective in improving the leaf pigments, proline, soluble sugar, total proteins, and all free amino acids. Additionally, the same treatment remained unmatched in terms of antioxidant activity compared to lower doses of foliar-applied Si. Moreover, VAM was recorded to be at peak under 20 ppm Si treatment. Thus, these encouraging findings may serve as a baseline to develop Si foliar application as a biologically viable mitigation strategy for maize grown in Cd toxicity soils. Overall, the exogenous application of Si helpful for reducing the uptake of Cd in maize and also improving the mycorrhizal association as well as the philological mechanism and antioxidant activities in plant under cadmium stress conditions. Also, future studies must test more doses concerning to varying Cd stress levels along with determining the most responsive crop stage for Si foliar application.

Exogenous application of low and high molecular weight organic acids differentially affected the uptake of cadmium in wheat-rice cropping system in alkaline calcareous soil.

Anthropogenic cadmium (Cd) in arable soils is becoming a global concern due to its harmful effects on crop yield and quality. The current study examined the role of exogenously applied low molecular weight organic acids (LMWOAs) including oxalic acid (OxA), tartaric acid (TA) and high molecular weight organic acids (HMWOAs) like citric acid (CA) and humic acid (HA) for the bioavailability of Cd in wheat-rice cropping system. Maximum increase in root dry-weight, shoot dry-weight, and grain/paddy yields was recorded with HA for both crops. The HA significantly decreased AB-DTPA Cd in contaminated soils which remained 41% for wheat and 48% for rice compared with their respective controls. The minimum concentration of Cd in roots, shoots and grain/paddy was observed in HA treatment in both crops. The organic acids significantly increased the growth parameters, photosynthetic activity, and relative leaf moisture contents for both wheat and rice crops compared to that with the contaminated control. Application of OxA and TA increased the bioavailability of Cd in soils and plant tissues while CA and HA decreased the bioavailability of Cd in soils and plants. The highest decrease in Cd uptake, bioaccumulation, translocation factor, immobilization, translocation, harvest, and health risk indices were observed with HA while maximum increase was recorded with OxA for both wheat and rice. The results concluded that use of HMWOAs is effective in soil Cd immobilization being maximum with HA. While LMWOAs can be used for the phytoextraction of Cd in contaminated soils having maximum potential with OxA.

Foliar application of silicon-based nanoparticles improve the adaptability of maize (Zea mays L.) in cadmium contaminated soils.

Heavy metals (HMs) especially cadmium (Cd) absorbed by the roots of crop plants like maize have emerged as one of the most serious threats by causing stunted plant growth along with disturbing the photosynthetic machinery and nutrient homeostasis process. A trial was conducted for inducing Cd stress tolerance in maize by exogenous application of silicon nanoparticles (SiNPs) using five doses of SiNPs (0, 100, 200, 300, and 400 ppm) and three levels of Cd (0, 15, and 30 ppm) for maize hybrid (SF-9515). The response variables included morphological traits and biochemical parameters of maize. The results indicated that Cd level of 30 ppm remained the most drastic for maize plants by recording the minimum traits such as shoot length (39.35 cm), shoot fresh weight (9.52 g) and shoot dry weight (3.20 g), leaf pigments such as chlorophyll a (0.55 mg/g FW), chlorophyll b (0.27 mg/g FW), total contents (0.84 mg/g FW), and carotenoid contents (0.19 µg/g FW). Additionally, the same Cd level disrupted biochemical traits such as TSP (4.85 mg/g FW), TP (252.94 nmol/g FW), TSAA (18.92 µmol g-1 FW), TSS (0.85 mg/g FW), and antioxidant activities such as POD (99.39 min-1 g-1 FW), CAT (81.58 min-1 g-1 FW), APX (2.04 min-1 g-1 FW), and SOD (172.79 min-1 g-1 FW). However, a higher level of Cd resulted in greater root length (87.63 cm), root fresh weight (16.43 g), and root dry weight (6.14 g) along with higher Cd concentration in the root (2.52 µg/g-1) and shoot (0.48 µg/g-1). The silicon nanoparticles (Si NPs) treatment significantly increased all measured attributes of maize. The highest value was noted of all the parameters such as chlorophyll a (0.91 mg/g FW), chlorophyll b (0.57 mg/g FW), total chlorophyll contents (1.48 mg/g FW), total carotenoid contents (0.40 µg/g FW), TSP (6.12 mg/g FW), TP (384.56 nmol/g FW), TSAA (24.64 µmol g-1 FW), TSS (1.87 mg/g FW), POD (166.10 min-1 g-1 FW), CAT (149.54 min-1 g-1 FW), APX (3.49 min-1 g-1 FW), and SOD (225.57 min-1 g-1 FW). Based on recorded findings, it might be inferred that higher levels of Cd tend to drastically reduce morpho-physiological traits of maize and foliage-applied silver nanoparticles hold the potential to ameliorate the adverse effect of Cd stress on maize.

Amylase as a Diagnostic Tool for Plunging Ranula: Clinical Series and Description of the Technique.

OBJECTIVES: This study describes a technique of measurement for neck cyst amylase content and reviews the experience of a tertiary referral center for cases of suspected plunging ranula. METHODS: A retrospective study was performed at the Manukau Surgical Center in Auckland, New Zealand. Patients with a possible diagnosis of plunging ranula based on clinical presentation and diagnostic aspiration of the cyst contents were included. Demographic data, imaging and laboratory findings were collected, along with findings from surgery and histology. The technique for measuring the amylase of the aspirated cyst contents was also carefully recorded. RESULTS: The 37 cases of confirmed plunging ranula included in this study had a submandibular cystic swelling that was aspirated. Imaging features consistent with a plunging ranula were seen in 89% of the study group. All cases had detectable levels of amylase of ≥3 U/L in the ranula contents. There was large variability (range: 5-560 U/L) in the concentration of amylase, with 70% of the cases demonstrating an amylase concentration below 200 U/L. Aspirates were typically described as viscous (87.5%) and yellow or straw-colored. CONCLUSION: The combination of clinical presentation, imaging and the presence of amylase in the cyst contents is diagnostic for plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:535-538, 2023.

Stibonic acids and related stibonate-phosphonate clusters: Synthesis, characterization and bioactivity evaluation.

The reaction of 4-(azobenzene)phenylstibonic acid with t-butylphosphonic acid led to the isolation of the tetranuclear oxo-hydroxo antimony cluster of formulae [(4-azobenzene-C6H4Sb)4(OH)4(tBuPO3)6] (C1). The reaction of (p-t-butyl phenyl stibonic acid with phenyl phosphonic acid resulted in the isolation of complex with formulae [(p-t-BuC6H4Sb)4(O)2(PhPO3)4(PhPO3H)4] (C2). Based upon the initial results from docking studies, parent stibonic acids, t-butyl-phenylstibonic acid, p-isopropylphenylstibonic acid, 4-azobenzenephenylstibonic acid, and the derived tetranuclear organoantimonate-phosphonate clusters were screened against different cancer cell lines, various Gram-positive and Gram-Negative bacteria and mycobacteria for possible bioactivity profile.

The Manukau Salivary Symptoms Score for Assessing the Impact of Sialendoscopy in Recurrent Obstructive Sialadenitis.

OBJECTIVE: To examine the Manukau Salivary Symptom Score (MSSS) questionnaire as a validated tool to assess obstructive sialadenitis-specific symptoms to both indicate disease severity and assess the outcome after sialendoscopic procedures. STUDY DESIGN: A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic chronic obstructive salivary gland disease (COSGD). SETTING: Department of Otolaryngology-Head and Neck Surgery at the Manukau Surgical Centre, Auckland, New Zealand, between June 2010 and September 2019. METHODS: A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic COSGD. Patients completed the MSSS preoperatively and at postoperative follow-up. Statistical tests were used to compare pre- and postoperative answers. Cronbach's α was used to measure internal consistency. Finally, construct validity was determined by comparing the 5-question MSSS questionnaire to the preexisting 20-question Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire. RESULTS: Postoperatively, patients had significant improvements in pain, eating, talking, swelling, and quality of life (P < .001). The MSSS questionnaire was found to have high internal consistency (α = 0.938). Questions in the MSSS had a very strong positive correlation with 3 COSS questions, a strong positive correlation with 8, a moderate positive correlation with 4, and a weak positive correlation with 1. Four COSS questions were not considered relevant and were not included in the MSSS questionnaire. CONCLUSION: The MSSS questionnaire is a simple, validated questionnaire that is useful for assessing the impact of sialendoscopy in patients with COSGD.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.

Patient Outcomes After Unsuccessful Endoscopic Sialolith Extraction.

OBJECTIVE/HYPOTHESIS: To evaluate clinical outcomes following failed endoscopic extraction of salivary calculi and to assess any relation between clinical outcome and calculi location, number, size, and mobility. If sialendoscopy fails to extract the calculus, subsequent spontaneous passage of the calculus out of the ductoglandular system or secondary effects of sialendoscopy could mitigate the clinical impact of a residual sialolithiasis. STUDY DESIGN: Prospective observational study. METHODS: Prospective comparative study of endoscopic procedures for sialolithiasis performed in the Manukau Surgery Center, in Auckland, New Zealand, from 2010 to 2020. The recurrent symptoms and the variables related to the need for additional surgical intervention for salivary calculi were analyzed. RESULTS: Among the 465 sialendoscopy procedures, 154 (33.1%) were for obstructive sialolithiasis. Among these, there were 30 (19.4%) with unsuccessful stone extraction with re-operation for these failures performed in 14 of the 27 failed submandibular cases (52%) and 2 of the 3 parotids (66.7%). Location of calculi was a significant factor in predicting the need of further surgery. Patients with perihilar stones were 5 times more likely to have a failed procedure (P = .001). If the stone was intraglandular, the likelihood increased to 8.5 times (P = .005). The likelihood for a revision procedure increased almost 11 times if the stone was intraglandular (P = .004). Calculi size, mobility, multiple calculi, and presence of concurrent stenosis did not correlate with need for further surgery. CONCLUSIONS: A significant proportion of "failed" sialendoscopy did not require further intervention. Stone location was a significant factor in predicting a failed procedure and the need for re-intervention. Laryngoscope, 132:1029-1033, 2022.

Optimization for biogenic microbial synthesis of silver nanoparticles through response surface methodology, characterization, their antimicrobial, antioxidant, and catalytic potential.

Silver is a poisonous but precious heavy metal that has widespread application in various biomedical and environmental divisions. Wide-ranging usage of the metal has twisted severe environmental apprehensions. Henceforth there is a cumulative call for the progress of modest, low-cost and, the ecological method for remediation of silver. In the present study, Bacillus cereus was isolated from contaminated soil. Various experimental factors like the amount of AgNO3, inoculum size, temperature, time, and pH were improved by using central composite design (CCD) grounded on response surface methodology (RSM). Optimized values for AgNO3 (1 mM) 10 ml, inoculum size (Bacillus cereus) 8.7 ml, temperature 48.5 °C, time 69 h, and pH 9 showed in the form of optimized ramps. The formed nanoparticles stayed characterized by UV-visible spectrophotometer, Scanning Electron Microscopy, Fourier transform infra-red spectrometry, particle size analyzer, and X-ray diffraction. The particle size ranges from 5 to 7.06 nm with spherical form. The antimicrobial effectiveness of synthesized nanoparticles was tested contrary to five multidrug resistant microbial strains, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Salmonella enterica, Porteus mirabilis by disc diffusion method. The minimum inhibitory concentrations and minimum lethal concentrations were detected by the broth macro dilution method. 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) was used to check the free radical scavenging ability of biogenic silver nanoparticles. Similarly, anti-radical activity was checked by 2,2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid (ABTS) with varying time intervals. Catalytic potential of biosynthesized silver nanoparticles was also investigated.

The synergistic strategy and microbial ecology of the anaerobic co-digestion of food waste under the regulation of domestic garbage classification in China.

With the implementation of new domestic garbage classification policy in China, attention is growing to improve the treatment efficiency of municipal 'wet' waste. Combing with the new regulation, the synergistic strategy and the microbial ecology of the anaerobic co-digestion (AcoD) of cooked food waste (CFW), uncooked food waste (UCFW) and rice straw (RS) were analyzed in current study. Results showed that the maximum cumulative methane yield (CMY) and synergic index were obtained when CFW and UCFW were mixed at the ratio of 1:1 (based on volatile solid content). The highest CMY 452.94 ± 0.99 mL/g-VS was obtained when the ratio of CFW, UCFW and RS was 0.81:0.09:0.10, which was 16.29%, 36.20% and 121.84% higher than their mono-digestion, respectively. The AcoD promoted the methane potential by prolonging the release time of organic matter and slowing down the hydrolysis rate. Furthermore, the AcoD increased the species diversification and relative abundance of fermentation bacteria in digesters, and Methanosaeta predominated the methanogen communities. This study demonstrated a clean and sustainable AcoD strategy for safe disposal of urban food waste and revealed the variation of microbial community, which can provide a base for efficient bioenergy recovery from urban domestic garbage.

Bilateral Plunging Ranulas in South Auckland: Evidence for a Genetic Basis.

OBJECTIVES: We present a series of bilateral plunging ranula patients to examine the etiology, diagnosis, treatment, and prognosis of this condition. METHODS: A retrospective chart review was performed on all cases of plunging ranula treated at the Department of Otolaryngology-Head and Neck Surgery, Counties Manukau District Health Board, New Zealand, between 2001 and 2019. RESULTS: There were 17 patients with bilateral plunging ranulas from a total of 187 plunging ranula patients. Eight patients were of Pacific Island descent; six were Maori; and three were Asian. There were no European patients with bilateral plunging ranulas. There were three types of bilateral plunging ranula patients: 1) Metachronous plunging ranulas-Five patients presented with a unilateral plunging ranula with no evidence of a contralateral plunging ranula on initial imaging. Despite negative contralateral imaging findings, these patients developed a clinically evident contralateral plunging ranula 21 to 61 months later. 2) Synchronous plunging ranulas detected on imaging-Eight patients presented with a clinically evident unilateral plunging ranula but also had a contralateral plunging ranula detected on imaging. 3) Clinically evident synchronous plunging ranulas-Four patients presented with bilateral clinically evident plunging ranulas, which were also evident on imaging. Twelve patients underwent bilateral transoral sublingual gland excision and plunging ranula evacuation. CONCLUSION: All patients with a unilateral plunging ranula should be advised of the potential for developing contralateral disease, and this should be emphasized in patients of Pacific Island, Maori, and Asian descent. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:73-77, 2021.

Do Postoperative Oral Corticosteroids Improve Results After Sialendoscopy for Ductal Stenosis?

OBJECTIVES: This study aims to review the effects of short- and long-term oral administration of postoperative corticosteroids in patients undergoing sialendoscopy for the treatment of obstructive sialadenitis due to ductal stenosis. STUDY DESIGN: Prospective comparative study. METHODS: A prospective observational study was conducted at Manukau Surgical Center in Auckland, New Zealand, where patients undergoing sialendoscopic surgery for recurrent obstructive sialadenitis due to ductal stenoses were reviewed. Univariable and multivariable analysis, and also logistic regression were performed to identify variables correlated with the likelihood of the need for revision surgery for persistent or recurrent symptoms. RESULTS: In this study, sialendoscopy was performed in 142 patients: 162 parotid glands (86.6%) and 25 submandibular glands (13.4%). Postoperative oral steroids were prescribed for 48 patients (34%); 19 (13%) were prescribed for less than 7 days and 29 (20%) for more than 7 days. In total, 33 patients (23.2%) required a revision sialendoscopy during follow-up due to recurrence of symptoms. Oral steroids prescribed for more than 7 days after a sialendoscopy reduced the likelihood of a revision procedure by 93% when compared with patients who did not receive this medication, and by 96% when compared with patients who received steroids for less than 7 days. CONCLUSION: The results showed that in our population oral administration of corticosteroids for more than 7 days after sialendoscopy for the treatment of recurrent obstructive sialadenitis due to ductal stenosis markedly reduced the need for later revision surgery. Routine use of corticosteroids for more than 7 days is recommended after sialendoscopy in patients with ductal stenosis. LEVEL OF EVIDENCE: II Laryngoscope, 131:E1503-E1509, 2021.

Adaptive Molecular Evolution of AKT3 Gene for Positive Diversifying Selection in Mammals.

The V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) gene is of the serine/threonine-protein kinase family and influences the production of milk fats and cholesterol by acting on the sterol administrative area restricting protein (SREBP). The AKT3 gene is highly preserved in animals, and during lactation in cattle, its expression increases. The AKT3 gene is expressed in the digestive system, mammary gland, and immune cells. A phylogenetic investigation was performed to clarify the evolutionary role of AKT3, by maximum probability. The AKT3 gene sequence data of various mammalian species was evident even with animals undergoing breeding selection. From 39 mammalian species studied, there was a signal of positive diversifying selection with Hominidae at 13Q, 16G, 23R, 24P, 121P, 294K, 327V, 376L, 397K, 445T, and 471F among other codon sites of the AKT3 gene. These sites were codes for amino acids such as arginine, proline, lysine, and leucine indicating major roles for the function of immunological proteins, and in particular, the study highlighted the importance of changes in gene expression of AKT3 on immunity.

Residual effects of frequently available organic amendments on cadmium bioavailability and accumulation in wheat.

Wheat (Triticum aestivum L.) cultivation in cadmium (Cd) polluted soil is a core concern to food quality and food security all over the world. Cadmium toxicity is mainly associated with a Cd influx from contaminated soils to human via grain consumption. Organic amendments are widely used for Cd immobilization and enhancement in plant growth, but the residual effects of these amendments are mostly unknown. The present study addressed the long-term effects of organic amendments in contaminated soils by evaluating their residual effects on 3rd crop (wheat) in the sequence. Initially six organic amendments viz. rice husk biochar (RHB), wheat-straw biochar (WSB), cotton-stick biochar (CSB), poultry manure (PM), press mud (PrMd) and farm manure (FM) were applied once at a rate of 2% in Cd (50 mg kg-1) contaminated soil with wheat-rice rotation. After the harvest of wheat and rice crops, wheat (Var. Galaxy) was again grown in the same pots. Results revealed that plants grown under Cd stress (without any amendment) contain more tissue (root, shoot and grain) and soil AB-DTPA extractable Cd. The soil amended with RHB has shown lowest AB-DTPA extractable Cd (69% lower than control). Similarly, RHB application has significantly reduced wheat root, shoot and grain Cd concentrations compared to control and other amendments. Results have confirmed the effectiveness of RHB residual contents as an active amendment for restriction of Cd in non-bioavailable pool of soil and better growth and yield of wheat.

Influence of bcr-3 PML-RARα transcript on outcome in Acute Promyelocytic Leukemia patients of Kashmir treated with all-trans retinoic acid and/or arsenic tri-oxide.

AIMS: Distinct types of PML-RARα hybrid transcripts viz bcr-1, bcr-2 and bcr-3 result from translocation between chromosomes 15 and 17 t(15;17) in Acute Promyelocytic Leukemia patients. We aimed to determine the frequencies of the PML-RARα transcripts and FLT3-ITD mutations in APL patients to evaluate their prognostic implications and also to analyze their impact on disease outcome. MAIN METHOD: RT-PCR and Rq-PCR were adopted for transcript typing and quantitation of PML-RARα transcripts while FLT3-ITD was detected by PCR in APL patients. KEY FINDINGS: PML-RARα bcr-1, bcr-2 and bcr-3 transcripts were found in 26, 3 and 16 cases respectively. 64.4% patients achieved complete remission, 22.2% expired early wherein majority of the cases expressed bcr-3 transcript (p = 0.03). 50% relapse rate was observed in patients with bcr-3 transcripts. Multivariate analysis showed expression of bcr-3 transcript associated with early death (p = 0.027) and increased relapse risk (P = 0.046). Patients expressing bcr-3 hybrid transcript showed lowest OS of 28.0 months (±â€¯5.26) (p = 0.027). FLT3-ITD mutation was detected in 5 (11.1%) patients and presence of these mutations was not associated either with PML-RARα transcripts or with disease outcome. SIGNIFICANCE: bcr-3 transcript has a more lethal outcome and is also associated with frequent relapse risk in APL patients of our region.