Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

BACKGROUND:  Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism.  Method: A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. RESULTS: Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. CONCLUSION: A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Bifunctional oxidase-peroxidase mimicking Fe-Ce MOF on paper-based analytical devices to intensify luminol chemiluminescence: Application for measuring different sugars with a smartphone readout.

This study presents a potent paper-based analytical device (PAD) for quantifying various sugars using an innovative bi-nanozyme made from a 2-dimensional Fe/Ce metal-organic framework (FeCe-BTC). The MOF showed excellent bifunctional peroxidase-oxidase activities, efficiently catalyzing luminol's chemiluminescence (CL) reaction. As a peroxidase-like nanozyme, FeCe-BTC could facilitate the dissociation of hydrogen peroxide (H2O2) into hydroxyl radicals, which then oxidize luminol. Additionally, it was also discovered that when reacting with H2O2, the MOF turns into a mixed-valence MOF, and acts as an oxidase nanozyme. This activity is caused by the generated Ce4+ ions in the structure of MOF that can directly oxidize luminol. The MOF was directly synthesized on the PAD and cascaded with specific natural enzymes to establish simple, rapid, and selective CL sensors for the measurement of different sugars. A cell phone was also used to record light intensities, which were then correlated to the analyte concentration. The designed PAD showed a wide linear range of 0.1-10 mM for glucose, fructose, and sucrose, with detection limits of 0.03, 0.04, and 0.04 mM, respectively. It showed satisfactory results in food and biological samples with recovery values ranging from 95.8 to 102.4 %, which makes it a promising candidate for point-of-care (POC) testing for food control and medicinal purposes.

A diagnosis of syphilis following a radical circumcision for suspected penile cancer.

We present a case of a 70-year-old gentleman who was referred to our tertiary 2-week-wait penile cancer clinic with a penile mass that was ulcerated, painful and discharging. This was suspicious for penile cancer and a radical circumcision was performed to remove the diseased foreskin en bloc with the lesion that was arising from the inner foreskin. Histopathology did not reveal cancer; however, we identified spirochaetes in keeping with syphilis. This was confirmed on serology. The patient was referred to the genitourinary medicine team and treated with antibiotics. This case demonstrates a rare presentation of genital syphilis in an elderly gentleman initially referred with concerns of penile cancer. Although, rare, especially in this age group, syphilis should be considered as a differential diagnosis in a patient presenting with an ulcerated, discharging, firm penile mass, especially given that the incidence of syphilis has been rising in recent years.

Modified Frailty Index as a Predictor of Adverse Outcomes in Elective Primary Hip and Knee Replacement Surgery Patients at a Tertiary Care Hospital in Pakistan: A Cross-Sectional Study.

Objective The objective was to evaluate the modified frailty index as a predictor of early (within 30 days) postoperative complications in total joint arthroplasty patients, in a low middle-income country. Material and methods A cross-sectional study was carried out which included patients with ages ranging from 23 to 86 years, who underwent elective primary Total Hip or Knee Arthroplasties (TKA or THA) between December 2021 and February 2023. Modified frailty index (mFI-5) was calculated and 30-day morbidity and mortality were recorded. Post-operative complications were categorized as either surgical or medical and recorded. Results A total of 175 patients were included, amongst whom the majority were females (68.6%, n=120) and the mean age was 60.5 ± 13.2 years. 85 patients (48.6%) had a mFI-5 score of one while 48 patients (27.4%) had a score of two. Superficial surgical site infection was the most common complication overall in 6 patients (3.4%); however, no case of prosthetic joint infection was noted. Deep vein thrombosis (DVT) was the most common medical complication (1.7%, n=3). 5 patients (2.9%) required re-admission and two mortalities were recorded within the 30-day interval. A significant association was noted between post-operative surgical complications and mFI-5 score (p-value = < 0.001), with the risk of complications increasing with a higher mFI-5 score. Smoking was noted to be a risk factor for post-operative medical complications as well as 30-day mortality. Conclusion The current study shows that the mFI-5 index can effectively be used as a predictor of postoperative complications in the South Asian region such as Pakistan. This should be calculated routinely and can be used as a tool for pre-operative assessment and counseling.

Systemic Amyloid A Protein Amyloidosis With Gastrointestinal Involvement.

Systemic amyloidosis is a multiorgan deposition of misfolded amyloid protein fibrils. The systemic amyloid A protein (AA) amyloidosis type predominantly involves the kidney and is mostly an under-recognized complication among persons who inject drugs. Gastrointestinal involvement in systemic AA amyloidosis that is associated with illicit drug use is uncommon. In this report, we present a case of a 40-year-old man with history of injection drug use, recurrent skin and soft-tissue infection, and renal AA amyloidosis that presented with painless bloody bowel movement, which initially resolved with conservative management. Upon further evaluation, the patient was found to have empyema that required antibiotic therapy and bilateral pleural drain. His hospital course was further complicated by multiple episodes of hematochezia requiring gastrointestinal consultation. Subsequent gastrointestinal biopsy revealed amyloid deposit.

Rate and Predictors of Patient Satisfaction After Total Joint Arthroplasty: A Cross-Sectional Study in a Low-to-Middle-Income Country.

Objective This study aimed to assess the rate of patient satisfaction after primary total joint arthroplasty (TJA) using a validated satisfaction measure. Materials and methods A cross-sectional study was conducted, including all patients who underwent primary TJA between December 2021 and February 2023. The age of the study population was found to range from 23 to 86 years. Patient satisfaction was assessed using a validated tool comprising four questions and a quality of life (QoL) question. Results A total of 197 patients were included, with a mean age of 60.9 ± 12.7 years. Total knee replacement (TKR) was performed in 124 patients (62.9%), and total hip replacement (THR) in 73 patients (37.1%). The mean patient satisfaction score was 86.6 ± 14.4 out of a maximum of 100. A significant negative correlation was observed between the Charlson Comorbidity Index (CCI) and the overall satisfaction score (p-value = 0.029). The majority of the patients (52.3%, n = 103) answered that their QoL had greatly improved, and a similar level of improvement was noted in elderly vs. adult patients (p-value = 0.17). A significantly higher proportion of male patients reported improvement more than they ever expected compared to female patients, the majority of whom reported their QoL was greatly improved (p-value = 0.025). Conclusion Total joint arthroplasty has been shown to achieve good patient satisfaction and an improvement in QoL. However, an increased comorbidity index and female gender were identified as factors for reduced satisfaction. Hence, it is recommended to consider these factors and counsel patients accordingly based on local patient data.

FeS2 nanosheets-luminol-O2 chemiluminescence method for determination of venlafaxine hydrochloride, imipramine hydrochloride, and cefazolin sodium.

This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol-O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10-7 to 1.00 × 10-3 mol L-1, 1.00 × 10-7 to 1.00 × 10-4 mol L-1, and 4.00 × 10-6 to 2.00 × 10-4 mol L-1 with detection limits (3σ) of 3.54 × 10-7, 1.08 × 10-8, and 2.63 × 10-6 mol L-1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.

Temperature-dependent failure of atomically thin MoTe2.

CONTEXT: In this study, we investigated the mechanical responses of molybdenum ditelluride (MoTe2) using molecular dynamics (MD) simulations. Our key focus was on the tensile behavior of MoTe2 with trigonal prismatic phase (2H-MoTe2) which was investigated under uniaxial tensile stress for both armchair and zigzag directions. Crack formation and propagation were examined to understand the fracture behavior of such material for varying temperatures. Additionally, the study also assesses the impact of temperature on Young's modulus and fracture stress-strain of a monolayer of 2H-MoTe2. METHOD: The investigation was done using molecular dynamics (MD) simulations using Stillinger-Weber (SW) potentials. The tensile behavior was simulated for temperature for 10 K and then from 100 to 600 K with a 100-K interval. The crack propagation and formation of 10 K and 300 K 2H-MoTe2 for both directions at different strain rates was analyzed using Ovito visualizer. All the simulations were conducted using a strain rate of 10-4 ps-1. The results show that the fracture strength of 2H-MoTe2 in the armchair and zigzag direction at 10 K is 16.33 GPa (11.43 N/m) and 13.71429 GPa (9.46 N/m) under a 24% and 18% fracture strain, respectively. The fracture strength of 2H-MoTe2 in the armchair and zigzag direction at 600 K is 10.81 GPa (7.56 N/m) and 10.13 GPa (7.09 N/m) under a 12.5% and 12.47% fracture strain, respectively.

Palmer Nodular Fasciitis Harboring a Novel SREBF1::USP6 Fusion Gene.

The diagnosis of low-grade fibroblastic/myofibroblastic tumors of acral sites can be challenging. These tumors encompass a diverse group of neoplasms with a spectrum of biologic potential ranges from benign to overtly malignant. They often demonstrate significant clinical, radiologic, and immunophenotypic overlap, in which the molecular phenotype may play an important diagnostic role to arrive at the final diagnosis. Herein, we report a case of soft tissue mass lesion presented on the palm of an adult patient for four months. Histologically, the tumor consisted of primarily low-grade spindle cells expressing smooth muscle actin. Molecular testing revealed a novel SREBF1::USP6 fusion gene, confirming the final diagnosis of nodular fasciitis and ultimately expanding its molecular profile. This case highlights the diagnostic value of single, cost-effective, targeted molecular panel to arrive at an accurate diagnosis and provide helpful therapeutic information.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Non-Small Cell Lung Carcinoma With Clear Cell Features and FGFR3::TACC3 Gene Rearrangement : Clinicopathologic and Next Generation Sequencing Study of 7 Cases.

Seven cases of primary lung tumors characterized histologically by clear cell morphology and a distinctive FGFR3::TACC3 gene rearrangement are described. The tumors arose in 4 women and 3 men, aged 47 to 81 years (mean=68). They occurred in peripheral locations, predominantly subpleural, and ranged in size from 1.4 to 6.5 cm (mean=4.1 cm). All tumors showed a solid growth pattern with abundant central areas of necrosis and marked nuclear pleomorphism. The tumors demonstrated clear cell histology, with large cohesive tumor cells displaying atypical nuclei and abundant clear cytoplasm. Immunohistochemical stains identified a squamous phenotype in 5 cases and an adenocarcinoma phenotype in 2 cases. One case was a squamous cell carcinoma with focal glandular component, and one of the squamous cell carcinomas showed focal sarcomatoid changes. Next generation sequencing identified FGFR3::TACC3 gene rearrangements in all 7 cases. One case demonstrated a concurrent activating FGFR3 mutation and a second case demonstrated concurrent FGFR3 amplification. Two cases harbored a concurrent KRAS G12D mutation. One case harbored both KRAS and EGFR mutations, and 1 case had a concurrent TP53 mutation. Non-small cell lung carcinoma harboring FGFR3::TACC3 gene rearrangements is extremely rare, and this rearrangement may potentially be enriched in tumors that demonstrate clear cell histology. Identification of FGFR3::TACC3 in patients with lung carcinomas with clear cell features may be of importance as they could potentially be candidates for therapy with tyrosine kinase inhibitors.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Beyond the outdoors: indoor air quality guidelines and standards - challenges, inequalities, and the path forward.

In the last few decades, indoor air quality (IAQ) has become a major threat to public health. It is the fifth leading cause of premature death globally. It has been estimated that people spend ∼90 % of their time in an indoor environment. Consequently, IAQ has significant health effects. Although IAQ-related standards and guidelines, policies, and monitoring plans have been developed in a few countries, there remain several global inequalities and challenges. This review paper aims to comprehensively synthesize the current status of widely accepted IAQ guidelines and standards. It analyzes their global implementation and effectiveness to offer insights into challenges and disparities in IAQ policies and practices. However, the complexity of domestic environments and the diversity of international standards impede effective implementation. This manuscript evaluates international, national, and regional IAQ guidelines, emphasizing similarities and differences. In addition, it highlights knowledge gaps and challenges, urging the international scientific community, policymakers, and stakeholders to collaborate to advance IAQ standards and guidelines. The analysis evaluates the efficacy of guidelines, identifies deficiencies, and offers recommendations for the future of domestic air quality standards.

Risk Stratification of Differentiated Thyroid Cancer: A Single-Center Study in Basrah.

Background Differentiated thyroid cancer is a common endocrine cancer; most of it has an indolent course and favorable outcomes, with a subset of patients having the risk of disease recurrence, which can be assessed using the fixed American Thyroid Association (ATA) risk stratification system or the dynamic response to therapy risk stratification that can be modified during patients follow-up. Aim The aim of this article is to assess the risk stratification of patients having differentiated thyroid cancer. Methods This is a retrospective cross-sectional study in which we evaluated medical records of 75 patients having differentiated thyroid cancer to assess the baseline ATA risk of recurrence and compared it to the results of dynamic risk stratification in response to therapy at 6-12 months post-surgery and at the last visit. Thyroglobulin level, anti-thyroglobulin antibody, thyroid ultrasound, and cytopathological examination were used to determine dynamic response to therapy and divided subjects into four groups: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), and indeterminate response (IR). Results At baseline, 55 patients had low risk, 14 patients had intermediate risk, and six patients had high risk. At 6-12 months post-surgery, in the low-risk group, ER, BIR, and IR responses were observed in 56.4%, 5.5%, and 38.2% of patients, respectively, and none of them exhibited SIR. In the intermediate-risk group, ER, BIR, and IR responses were observed in 57.1%, 21.4%, and 21.4% of patients, respectively, and none exhibited SIR. Among the high-risk group, two patients had ER, two patients had BIR, one patient had IR, and one patient had SIR. At the last visit, ER, BIR, and IR were observed in 65.5%, 9.1%, and 25.5% of low-risk patients, respectively, and no patient developed SIR. In the intermediate-risk group, ER, BIR, and IR were observed in 50%, 21.4%, and 28.6% of patients, respectively, and no patients developed SIR. Among the high-risk group, three patients achieved ER, one had BIR, one had IR, and one had SIR. Conclusion Most of the differentiated thyroid cancers in this study are low-risk. Dynamic risk stratification appears to be an effective tool in the follow-up of this population of patients having differentiated thyroid cancer.

Acute Pancreatitis Following Percutaneous Mechanical Thrombectomy of Left Common Iliac Vein.

While parental or oral anticoagulation remains a mainstay of therapy for thrombosis, in sporadic clinical situations, percutaneous mechanical thrombectomy is favored. Percutaneous mechanical thrombectomy is a well-tolerated subtype of catheter-directed intervention resulting in thrombus breakdown and removal. This procedure combines endovascular mechanical thrombectomy in combination with pharmacologic thrombolysis allowing for a significant reduction in procedure time. Similar to other catheter-based procedures, common complications include hemorrhage, dissection, pseudoaneurysm, and perforations. Acute pancreatitis, in contrast, is a rare complication of percutaneous mechanical thrombectomy with only limited cases reported and is hypothesized to occur secondary to release of heme byproducts. Here, we present a case of acute pancreatitis following outpatient percutaneous mechanical thrombectomy of the left common iliac vein that ultimately required hospitalization, intensive care unit (ICU) admission, and standard medical management for pancreatitis.

A dual-targeting nanobiosensor for Gender Determination applying Signal Amplification Methods and integrating Fluorometric Gold and Silver Nanoclusters.

A dual-targeting nanobiosensor has been developed for the simultaneous detection of AMELX and AMELY genes based on the different fluorescence signals emitted from gold and silver nanoclusters, AuNCs and AgNCs respectively. In our design, both catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) have been used as isothermal, enzyme-free and simple methods for signal's amplification. The working principle is based on the initiation of a cascade of CHA-HCR reactions when AMELX is present, in which AuNCs, synthesized on the third hairpin, are aggregated on the surface of the dsDNA product, performing the phenomenon of aggregation induced emission (AIE) and enhancing their fluorescence signal. On the other hand, the presence of the second target, AMELY, is responsible for the enhancement of the fluorescence signal corresponding to AgNCs by the same phenomenon, via hybridizing to the free end of the dsDNA formed and at the same time to the probe of silver nanoclusters fixing it closer to the surface of the dsDNA product. Such a unique design has the merits of being simple, inexpensive, specific and stable and presents rapid results. The detection limits of this assay for AMELX and AMELY are as low as 3.16 fM and 23.6 fM respectively. Moreover, this platform showed great performance in real samples. The design has great promise for the application of dual-targeting nanobiosensors to other biomarkers.

A large dermoid cyst of the spermatic cord.

Dermoid cysts of the spermatic cord are rare, with only a few adult cases published in the literature. We report a patient with a 10cm inguinal mass referred to us for a suspected paratesticular sarcoma. Imaging suggested a cyst but, due to the recent increase in size, the cyst contents were evacuated and the cyst wall was biopsied. Histopathology revealed a dermoid cyst, which is a benign variant of cystic teratomas. Histopathological examination was required here due to the uncertainty. Careful interpretation was required, as cystic teratomas very occasionally undergo a malignant transformation.

AuNRs attached TiO2 NPs modified by cobalt-imidazolate frameworks as exceptional materials to improve the energy conversion efficiency of dye-sensitized solar cells.

This work reports a significant improvement in both the open-circuit voltage (VOC) and current density (J) of dye-sensitized solar cells (DSSCs) using gold nanorod-modified TiO2 nanoparticles (TiO2/AuNRs) together with a cobalt-imidazolate framework (ZIF-67) as an efficient photoanode. It was demonstrated that adding ZIF-67 (8 wt%) to TiO2 NPs increased the VOC by 160 mV and J by 2.5 times. This observation was described based on the significant increase in the amount of adsorbed dye in the presence of highly porous ZIF-67, which boosts the photoanode's light harvesting. Modifying TiO2 NPs with AuNRs also caused a remarkable enhancement in J (∼ 2.8 times), which can be explained via electron transfer between the TiO2 conduction band and AuNRs. It can result in a more efficient inhibiting effect on the interfacial charge recombination processes in TiO2/AuNRs/ZIF-67 because of the formation of a Schottky barrier at the interface between TiO2 and Au. These effects were confirmed by the reduction in the photoluminescence intensity of TiO2 in the presence of AuNRs. More reduction in the photoluminescence intensity was observed when ZIF-67 was added. The prepared photoanode showed an outstanding improvement in the overall efficiency of the DSSC (η) to 8.38% compared to the bare TiO2-based photoanode (1.83%). The notable improvement in the TiO2/AuNRs/ZIF-67 performance confirmed its practicality for high-efficiency DSSCs.