Noninvasive diagnostic biomarkers, genomic profiling, and advanced microscopic imaging in the early detection and characterization of Naegleria fowleri infections leading to primary amebic meningoencephalitis (PAM).

This review delves into the strategies for early detection and characterization of Naegleria fowleri infections leading to primary amoebic meningoencephalitis (PAM). The study provides an in-depth analysis of current diagnostic approaches, including cerebrospinal fluid analysis, brain tissue examination, immunostaining techniques, and culture methods, elucidating their strengths and limitations. It explores the geographical distribution of N. fowleri, with a focus on regions near the equator, and environmental factors contributing to its prevalence. The review emphasizes the crucial role of early detection in PAM management, discussing the benefits of timely identification in treatment, personalized care, and prevention strategies. Genomic profiling techniques, such as conventional PCR, nested PCR, multiplex PCR, and real-time PCR, are thoroughly examined as essential tools for accurate and prompt diagnosis. Additionally, the study explores advanced microscopic imaging techniques to characterize N. fowleri's morphology and behavior at different infection stages, enhancing our understanding of its life cycle and pathogenic mechanisms. In conclusion, this review underscores the potential of these strategies to improve our ability to detect, understand, and combat N. fowleri infections, ultimately leading to better patient outcomes and enhanced public health protection.

"Veozah (Fezolinetant): A Promising Non-Hormonal Treatment for Vasomotor Symptoms in Menopause".

Vasomotor symptoms (VMS) are a common and distressing experience during menopause, affecting a significant portion of women. Hormone therapy (HT) has been the traditional treatment, but its limitations and potential risks have led to the search foar non-hormonal alternatives. Recently, the FDA approved Veozah (Fezolinetant) as a promising nonhormonal solution for moderate to severe VMS in menopause. Veozah, an innovative neurokinin 3 (NK3) receptor antagonist, targets the disrupted thermoregulation underlying VMS. It modulates neural activity within the thermoregulatory center by crossing the blood-brain barrier, offering relief from hot flashes and night sweats. Clinical trials, including SKYLIGHT 1TM, SKYLIGHT 2TM, and SKYLIGHT 4TM, have established Fezolinemtant's efficacy and safety profile. The recommended dosage of one 45 mg tablet per day demonstrates proportional pharmacokinetics, with generally mild side effects that require regular monitoring. Fezolinetant's oral availability makes it a convenient and accessible option for women seeking relief from VMS, potentially improving their overall well-being.

All-Dielectric Transreflective Angle-Insensitive Near-Infrared (NIR) Filter.

This paper presents an all-dielectric, cascaded, multilayered, thin-film filter, allowing near-infrared filtration for spectral imaging applications. The proposed design is comprised of only eight layers of amorphous silicon (A-Si) and silicon nitride (Si3N4), successively deposited on a glass substrate. The finite difference time domain (FDTD) simulation results demonstrate a distinct peak in the near-infrared (NIR) region with transmission efficiency up to 70% and a full-width-at-half-maximum (FWHM) of 77 nm. The theoretical results are angle-insensitive up to 60∘ and show polarization insensitivity in the transverse magnetic (TM) and transverse electric (TE) modes. The theoretical response, obtained with the help of spectroscopic ellipsometry (SE), is in good agreement with the experimental result. Likewise, the experimental results for polarization insensitivity and angle invariance of the thin films are in unison with the theoretical results, having an angle invariance up to 50∘.

A Novel Privacy Paradigm for Improving Serial Data Privacy.

Protecting the privacy of individuals is of utmost concern in today's society, as inscribed and governed by the prevailing privacy laws, such as GDPR. In serial data, bits of data are continuously released, but their combined effect may result in a privacy breach in the whole serial publication. Protecting serial data is crucial for preserving them from adversaries. Previous approaches provide privacy for relational data and serial data, but many loopholes exist when dealing with multiple sensitive values. We address these problems by introducing a novel privacy approach that limits the risk of privacy disclosure in republication and gives better privacy with much lower perturbation rates. Existing techniques provide a strong privacy guarantee against attacks on data privacy; however, in serial publication, the chances of attack still exist due to the continuous addition and deletion of data. In serial data, proper countermeasures for tackling attacks such as correlation attacks have not been taken, due to which serial publication is still at risk. Moreover, protecting privacy is a significant task due to the critical absence of sensitive values while dealing with multiple sensitive values. Due to this critical absence, signatures change in every release, which is a reason for attacks. In this paper, we introduce a novel approach in order to counter the composition attack and the transitive composition attack and we prove that the proposed approach is better than the existing state-of-the-art techniques. Our paper establishes the result with a systematic examination of the republication dilemma. Finally, we evaluate our work using benchmark datasets, and the results show the efficacy of the proposed technique.

Laser ablation assisted micropattern screen printed transduction electrodes for sensing applications.

In this work we present a facile method for the fabrication of several capacitive transduction electrodes for sensing applications. To prepare the electrodes, line widths up to 300 [Formula: see text]m were produced on polymethyl methacrylate (PMMA) substrate using a common workshop laser engraving machine. The geometries prepared with the laser ablation process were characterised by optical microscopy for consistency and accuracy. Later, the geometries were coated with functional polymer porous cellulose decorated sensing layer for humidity sensing. The resulting sensors were tested at various relative humidity (RH) levels. In general, good sensing response was produced by the sensors with sensitivities ranging from 0.13 to 2.37 pF/%RH. In ambient conditions the response time of 10 s was noticed for all the fabricated sensors. Moreover, experimental results show that the sensitivity of the fabricated sensors depends highly on the geometry and by changing the electrode geometry sensitivity increases up to 5 times can be achieved with the same sensing layer. The simplicity of the fabrication process and higher sensitivity resulting from the electrode designs is expected to enable the application of the proposed electrodes not only in air quality sensors but also in many other areas such as touch or tactile sensors.

A Profile of Colorectal Tumors Presenting as Emergency.

OBJECTIVE:  To determine the factors, management and outcome of colorectal tumors presenting at Emergency Department, Mayo Hospital, Lahore. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Accident & Emergency Department, Mayo Hospital, Lahore, from August 2017 to July 2019. METHODOLOGY: Conducted on 40 consecutive patients who presented in the Accident and Emergency Department, Mayo Hospital, Lahore; determined to have colon or rectal cancer as the cause of intestinal obstruction or perforation, were studied. Data was abstracted from patient charts. Studied variables included patient's demographic data, indication for admission, surgical procedure done, complications, histopathology and mortality rate. RESULTS: Forty patients underwent operations of colon and rectum during the study period. Mean age at presentation was 37.8 ± 16.7 years. Intestinal obstruction (75%) was the main presenting symptom. Ascending colon was the main site involved (50%), followed by recto-sigmoid mass (15%) and rectal mass (12.5%); 80% patients subjected to the stoma formation. Electrolyte imbalance and wound infection were the most common medical and surgical complications. Adenocarcinoma was the most common tumor on histopathology (92.5%). After surgery 87.5% patients survived and 12.5% patients expired. Factors significantly associated with worse outcome were greater ASA score (p=0.004), absence of screening colonoscopy in the past (p=0.013) and postoperative medical complications (p<0.001). CONCLUSION: Colorectal tumor cases continue to present in emergency in a high number. Male gender, young age and ascending colon cancers were more frequent among such cases. Most patients had to undergo stoma formation in emergency. Mortality is significantly associated with higher ASA score, absence of screening colonoscopy and postoperative medical complications. Key Words: Colorectal carcinoma, Adenocarcinoma, Ascending colon, Wound infection, Emergency, Young males, Screening colonoscopy, ASA score.

Surgical Outcome of Peripheral Vascular Injuries in Adults.

OBJECTIVE: To describe the management and outcome of adult patients after peripheral vascular injuries. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Accident & Emergency Department, Mayo Hospital Lahore, Pakistan, from January 2014 to December 2018. METHODOLOGY: All adult trauma patients (aged ≥13 years), who were admitted following injury to peripheral blood vessels regardless injuries, were included. Variables including patient data, mechanism of injury, vessel involved, injury severity score (ISS), surgical procedure etc. were retrospectively extracted from patient charts. Binary logistic and multinomial regression analyses were performed. The p-value <0.05 was considered significant for mortality and limb outcome. RESULTS: There were 117 patients, with mean age of 28.9±11.6 years. The commonest cause was blunt trauma (55.6%). The popliteal artery was most commonly involved (44.4%). Complete transection of artery was the most common type of injury (58.1%). The mean ISS was 17.2 ± 10. Reverse saphenous vein graft (RSVG) was the most common surgical repair (49.6%) procedure. Wound infection (17.1%) was the main complication. Limb salvage rate was 73.5% and mortality rate was 5.1%. Variables significantly influencing the limb outcome (amputated vs. salvaged) were duration of injury (p <0.001), concomitant body injury (p=0.009), ISS (p <0.001), surgical procedure (p <0.001), hemoglobin on presentation (p<0.001), number of blood transfusion (p=0.05) complications after surgery (p <0.001) and referral or not (p=0.001). Factors significantly associated with mortality were duration of injury (p=0.008), ISS (p = 0.002) and complications after surgery (p=0.011). CONCLUSION: Low hemoglobin on presentation, postoperative increased requirement of blood transfusions and having reverse saphenous graft as procedure were independent risk factors for amputation. ISS score and postoperative complications led to higher amputation and mortality rates after surgery. Key Words: Injury severity score (ISS), Glasgow coma scale (GCS), Reverse saphenous graft (RSVG), Fasciotomy, Popliteal artery, Mortality.

Nanostructured Color Filters: A Review of Recent Developments.

Color plays an important role in human life: without it life would be dull and monochromatic. Printing color with distinct characteristics, like hue, brightness and saturation, and high resolution, are the main characteristic of image sensing devices. A flexible design of color filter is also desired for angle insensitivity and independence of direction of polarization of incident light. Furthermore, it is important that the designed filter be compatible with the image sensing devices in terms of technology and size. Therefore, color filter requires special care in its design, operation and integration. In this paper, we present a comprehensive review of nanostructured color filter designs described to date and evaluate them in terms of their performance.

Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines.

An efficient and environmentally benign simple fusion reaction of 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (1a) or 3-chloro-6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)pyridazine (2a) with different aliphatic/aromatic amines have produced a series of novel pyrazolylpyridazine amines (4a-4c &5a-5m). All compounds exhibited moderate in vitro yeast α-glucosidase inhibition except m-chloro derivative 5g, which was found potent inhibitor of this enzyme with IC50 value of 19.27±0.005µM. The molecular docking further helped in understanding the structure activity relationship of these compounds including 5g.

In search of new α-glucosidase inhibitors: Imidazolylpyrazole derivatives.

Under three different reaction conditions (conventional heating, microwave irradiations and amino acid catalysis), a series of imidazolylpyrazoles (2a-2k) were synthesized in good to excellent yields from a mixture of three precursors: aryl(hetaryl)pyrazole-4-carbaldehydes (1a-1k), benzil and ammonium acetate. α-Glucosidase inhibition assay revealed a new class of highly potent agents wherein each compound displayed significant inhibitory potentials (in terms of percentage inhibition and relative IC50 values) as compared to that of the reference drug (Acarbose). Moreover, molecular modelling of most potent compounds 2h, 2j and 2k also helped in understanding the structure and activity relationship.

Conceptualizing a subtype of patients with chronic pain: The necessity of obtaining a history of sexual abuse.

Lifetime history of sexual abuse is estimated to range between 15% and 25% in the general female population. Cross-sectional studies have shown that sexual assault survivors frequently report chronic musculoskeletal pain and functional somatic syndromes. Treating chronic pain with opioids went from being largely discouraged to being included in standards of care and titrating doses until patients self-report adequate control has become common practice, with 8% to 30% of patients with chronic noncancer pain receiving opioids. In this clinical review, we will discuss the association between survivors of sexual assault and chronic pain/functional somatic syndromes. We will further review evidence-based treatment strategies for this "pain-prone phenotype."

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.

resumo Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6​​), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.

Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer's disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase.

This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast α-glucosidase than the reference compound acarbose (IC50 38.25±0.12µM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6±0.2µM) against α-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; α-glucosidase (IC50 32.2±0.3µM), AChE (IC50 50.2±0.8µM) and BChE (IC50 43.8±0.8µM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with α-glucosidase and AChE targets.

Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase.

A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC50 value ranging between 18.23±0.03 and 424.41±0.94µM when compared with the standard acarbose (IC50, 38.25±0.12µM). Compound (8) (IC50, 18.23±0.03µM) and compound (7) (IC50=36.75±0.05µM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC50, 38.25±0.12µM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of α-glucosidase inhibitors.

Triazinoindole analogs as potent inhibitors of α-glucosidase: synthesis, biological evaluation and molecular docking studies.

A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 µM when compared with the standard acarbose (IC50, 38.25±0.12 µM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 µM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.

Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes.

A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32±0.59 µM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

Novel pyridine-2,4,6-tricarbohydrazide derivatives: design, synthesis, characterization and in vitro biological evaluation as α- and ß-glucosidase inhibitors.

A range of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4h) were synthesized and its biological inhibition towards α- and ß-glucosidases was studied. Most of the compounds demonstrate to be active against α-glucosidase, and quite inactive/completely inactive against ß-glucosidase. A number of compounds were found to be more active against α-glucosidase than the reference compound acarbose (IC50 38.25±0.12µM); being compound 4d with the p-hydroxy phenyl motive the most active (IC50 20.24±0.72µM). Molecular modeling studies show the interactions of compound 4d with the active site of target α-glucosidase kinase.

α-Glucosidase and lipoxygenase inhibitory derivatives of cryptosporioptide from the endophytic fungus Cryptosporiopsis sp.

Two new cryptosporioptide-derived polyketides cryptosporioptides A (2) and B (3) were isolated from the extract of endophytic fungus Cryptosporiopsis sp. associated with the shrub, Viburnum tinus. The structures of the isolates were determined through spectral analysis including 1D NMR ((1)H, (13)C) and 2D NMR (HSQC, HMBC, COSY) techniques, HR-FAB-MS and by comparison with the reported data of cryptosporioptide (1). The relative stereochemistry was assigned with the help of NOESY analysis, the molecular model, and comparison of the optical rotation values with the reference compound 1.

Clinical manifestations of new versus recrudescent malaria infections following anti-malarial drug treatment.

BACKGROUND: Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. New infections are not considered malaria treatment failures and as a result, the prevention of subsequent episodes of malaria infection is not reported as a study outcome. However, in moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the next imminent infection. The clinical benefit of preventing new infections has never been compared to that of curing the initial infection. METHODS: Children enrolled in a sulphadoxine-pyrimethamine efficacy study in Blantyre, Malawi from 1998-2004 were prospectively evaluated. Six neutral microsatellites were used to classify new and recrudescent infections in children aged less than 10 years with recurrent malaria infections. Children from the study who did not experience recurrent parasitaemia comprised the baseline group. The odds of fever and anaemia, the rate of haemoglobin recovery and time to recurrence were compared among the groups. RESULTS: Fever and anemia were more common among children with parasitaemia compared to those who remained infection-free throughout the study period. When comparing recrudescent vs. new infections, the incidence of fever was not statistically different. However, children with recrudescent infections had a less robust haematological recovery and also experienced recurrence sooner than those whose infection was classified as new. CONCLUSIONS: The results of this study confirm the paramount importance of providing curative treatment for all malaria infections. Although new and recrudescent infections caused febrile illnesses at a similar rate, recurrence due to recrudescent infection did have a worsened haemological outcome than recurrence due to new infections. Local decision-makers should take into account the results of genotyping to distinguish new from recrudescent infections when determining treatment policy on a population level. It is appropriate to weigh recrudescent malaria more heavily than new infection in assessing treatment efficacy.

Relationship between chest lateral width, tube current, image noise, and radiation exposure associated with coronary artery calcium scanning on 320-detector row CT.

BACKGROUND: The relationship between chest lateral width, tube current, image noise, and radiation exposure on 320-detector row CT has not been reported. OBJECTIVE: We investigated the relationships between chest lateral width, estimated radiation exposure (DLPe), and image noise in 300 patients undergoing clinical coronary calcium scanning. METHODS: Patients undergoing coronary calcium scanning with 320-detector row CT (prospective, volumetric mode, 120 kV of tube voltage, 100-550 mA of tube current, 0.5-mm detector width) were grouped by chest lateral width (small, medium, and large) from anteroposterior topograms and 100 consecutive patients were selected from each group (n = 300). Tube current, DLPe, and noise were compared among groups with Kruskal-Wallis or one-way ANOVA. Phantom experiments were performed to evaluate the accuracy of calcium quantification as a function of size and tube current. RESULTS: Median tube current in small, medium, and large patients was 130, 200, and 250 mA, respectively (P < 0.0001). Despite the use of higher tube current settings, noise levels also increased with size (20.2 ± 4.5 HU, 22.0 ± 3.9 HU, and 25.1 ± 4.9 HU, respectively; global P < 0.001). DLPe was significantly higher with increasing size (54, 83, and 104 mGy · cm, respectively; P < 0.0001). Phantom experiments showed that 50-100 mA, 150-200 mA, and approximately 300 mA in small, medium, and large phantoms were associated with stable estimate of calcium. CONCLUSIONS: Increasing chest lateral width is associated with increasing radiation exposure and image noise. The use of 50-100 mA in small and 150-200 mA in medium patients is associated with acceptable noise and stable estimate of coronary artery calcium. In large patients, precise identification of individual calcified lesions remains difficult despite increasing tube current and radiation exposure.