Basic Investigations Research Articles

Stimulating social interest: The translational value of basic investigations into frontal cortex function

Fan etal. use electrical stimulation during a novel social interaction paradigm to demonstrate a role for the orbitofrontal cortex in directing social attention. Their results shed new light on the basic functions of the orbitofrontal cortex and have translational value in understanding circuit modulation for psychiatric disorders.

Thermoelectric generator for energy production from renewable sources

Thermoelectric generators (TEG) produce electrical energy from a temperature difference between the cold and hot side of TEG modules (Seebeck effect); in principle, they can be used at temperature differences greater than 3 K [1]. Thermoelectric energy generation is primarily known for supplying self-sufficient sensors or in exhaust systems of motor vehicle internal combustion engines [2], where high temperature differences of up to 700 K are used. In this paper, basic investigations are carried out in order to expand the power range of thermoelectric energy generation and their potential for the energy transition. To this end, the area of application should be expanded to include medium and small temperature differences. The output characteristic of a TEG module has a power maximum, which increases quadratically with the temperature difference and linearly with the module area. At a temperature difference of 40 K, an output of 250 W/m2 can be generated. A solar module can generate 150 W/m2 in full sunlight; this output is only available for 12 % of the year given the 1000 full-load hours of sunshine that are usual in our latitudes. A continuous thermoelectric energy source could provide energy all year. Under optimal conditions, an annual usage time of 5000 hours and a service life of 10 years, electricity production costs of around 10 Cents/kWh can be expected [3]. This price is quite comparable to other renewable energy sources (photovoltaics, wind).

Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). I. Drugs in preclinical and early clinical development.

For >30 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided a forum for the discussion of advances in the development of new therapies for seizures and epilepsy. The EILAT XVII conference took place in Madrid, Spain, on May 5-8, 2024. Participants included basic scientists and clinical investigators from industry and academia, other health care professionals, and representatives from lay organizations. We summarize in this article information on treatments in preclinical and in early clinical development discussed at the conference. These include AMT-260, a gene therapy designed to downregulate the expression of Glu2K subunits of kainate receptors, in development for the treatment of drug-resistant seizures associated with mesial temporal sclerosis; BHV-7000, a selective activator of heteromeric Kv7.2/7.3 potassium channels, in development for the treatment of focal epilepsy; ETX101, a recombinant adeno-associated virus serotype 9 designed to increase NaV1.1 channel density in inhibitory γ-aminobutyric acidergic (GABAergic) neurons, in development for the treatment of SCN1A-positive Dravet syndrome; GAO-3-02, a compound structurally related to synaptamide, which exerts antiseizure activity at least in part through an action on cannabinoid type 2 receptors; LRP-661, a structural analogue of cannabidiol, in development for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex; OV329, a selective inactivator of GABA aminotransferase, in development for the treatment of drug-resistant seizures; PRAX-628, a functionally selective potent sodium channel modulator with preference for the hyperexcitable state of sodium channels, in development for the treatment of focal seizures; RAP-219, a selective negative allosteric modulator of transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor regulatory protein γ-8, in development for the treatment of focal seizures; and rozanolixizumab, a humanized anti-neonatal Fc receptor monoclonal antibody, in development for the treatment of LGI1 autoimmune encephalitis. Treatments in more advanced development are summarized in Part II of this report.

A green and innovative approach to separate hexafluorophosphate from wastewater

Effluent derived from spent lithium-ion batteries (LIBs) electrolyte or discarded ionic liquids (ILs) is a potentially resource of hexafluorophosphate (PF6−) which can be recovered through solvent extraction. In this study, an efficient extraction approach was proposed to recover the hexafluorophosphate from solutions. A basic investigation on the interactions between extractants and hexafluorophosphate was firstly carried out using density functional theory (DFT), which demonstrated the stability of the extracted complex structure. The effects of extractant (Alamine336) and modifier, common anions and metallic ions in waste-streams, initial pH, and temperature on the extraction efficiency were explored. The results showed that 96.16 % of hexafluorophosphate could be extracted and transferred into organic phase using Alamine336/modifier as extractant under optimal conditions (0.15 mol/L of Alamine336 and 0.25 mol/L of modifier). The organic phase exhibited an excellent extraction capability of >95 % under optimal condition. Moreover, it was found that the use of sodium hydroxide as stripping reagent presented a superb stripping and cycling properties. Thermodynamic analysis and spectral data indicated that PF6− was extracted into the organic phase in the form of R3NH⋅PF6, which is a spontaneous exothermic process. The novel extraction method provides a broad application perspective for the removal and recovery of valuable hexafluorophosphate from aqueous system.

Assessing the Role of Transvaginal Sonography in Post-menopausal Bleeding: A Less Invasive Approach to Identify Endometrial Carcinoma.

Background Post-menopausal bleeding (PMB) is a very common complaint seen in current practice. Endometrial carcinoma (EC) commonly presents with PMB. Endometrial biopsy is the tool for definitive diagnosis, but it is invasive. Transvaginal sonography (TVS) is a non-invasive tool that can help us in the initial evaluation of such patients. Methods A prospective observational study was conducted on 76 women with PMB. TVS and histopathological study, along with basic evaluation and investigations, were performed on all participants, followed by necessary treatment and follow-up. Data collected were studied and statistically analyzed. Results A maximum of 27.63% (n=21) of patients had endometrial atrophy causing their PMB. Proliferative endometrium was observed in 21.06% (n=16) of cases, 13.15% (n=10) of women had secretory endometrium, 23.68% (n=18) had simple endometrial hyperplasia, 3.94% (n=3) had complex endometrial hyperplasia without atypia, and another 3.94% (n=3)had complex endometrial hyperplasia with atypia. Further classifying, women with benign hyperplasia included 27.63% (n=21) and those with atypical hyperplasia included 3.94% (n=3). Out of the 5.26% (n=4) patients diagnosed with EC on histopathology, TVS identified carcinoma in75% (n=3) cases. This indicates that the sensitivity and specificity of TVS in detecting EC are 75% and 100%, respectively. The positive predictive value (PPV) is 100%, the negative predictive value (NPV) is 98.63%, and the accuracy is 98.68%. Conclusion If the cut-off for endometrial thickness is set at 4 mm, then TVS proves to be an effective and reliable tool for screening and diagnosing EC. It can thus serve as a safe threshold to screen patients with PMB using TVS.

Clinical Spectrum of Dermatological Disorders at an Urban Health Center in East Delhi.

Dermatological disorders constitute a significant proportion of primary health care (PHC) setups. The pattern of dermatological disorders varies among different countries and different parts of the same country owing to climatic and geographical variations, level of education, access to health care, etc. To study the clinical spectrum of patients presenting with dermatological disorders at an urban health center (UHC) in East Delhi. To identify the various risk factors associated with dermatological disorders in study subjects. A total of 1,148 patients who reported skin diseases for the first time at the Dermatology Outpatient Clinic at UHC in East Delhi were recruited. Detailed demographic data, history, and examination and potential risk factors of skin diseases (socioeconomic status, level of education, occupation, comorbidities, and addictions) were recorded on a predesigned proforma. A total of 616 (53.7%) patients had infectious dermatoses and 532 (46.3%) had non-infectious dermatoses. Among the infectious dermatoses, fungal diseases (44.8%) were the most common followed by parasitic infections (31.17%) and bacterial infections (9.74%). Among the non-infectious group, eczematous disorders (28.01%) were the most common, followed by pigmentary disorders (21.62%) and acne (19.55%). A significant association between level of education, occupation, and comorbidities with the distribution of infectious and non-infectious dermatoses was found. As a significant proportion of patients with a vivid spectrum of dermatological disorders present at the PHC setups, therefore dermatologists supervise that specialty clinics should be held regularly at these centers along with the availability of all the basic investigations to aid diagnosis and management.

Mapping Theme Trends and Research Frontiers in Dexmedetomidine Over Past Decade: A Bibliometric Analysis.

Dexmedetomidine, an α2-adrenergic receptor (α2-AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers. Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1). The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology. Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications. Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications.

Recurrent symptomatic urolithiasis in a patient with cystic fibrosis.

A 6-month-old girl, previously diagnosed with cystic fibrosis (CF), was admitted to hospital for nephrolithiasis. Her parents were first-degree cousins. The patient underwent endoscopic stone management. Despite no family history of stones and medical treatment with potassium citrate, the patient developed recurrent renal stones and atypical urinary tract infections during follow-up. Basic investigations were all normal. Due to consanguinity and early presentation of nephrolithiasis, metabolic causes such as cystinuria and hyperoxaluria were considered. Cystinuria was excluded due to normal cystine levels. High urinary oxalate excretion was found as expected due to absorptive (secondary) hyperoxaluria in CF patients. An early stone burden in the patient with a history of medical treatment and consanguinity led us to perform a genetic testing. Genetic testing revealed a missense homozygous variant in exon 1 of the AGXT gene. The patient was diagnosed with primary hyperoxaluria type 1. Two rare life-threatening genetic diseases were found together in the same child.

Cardiac rehabilitation centers in Romania: Where are we now?

Purpose: In 2024, Romania is still facing a critical challenge with high cardiovascular disease mortality rates despite extensive research and policy initiatives. Our study sought to examine the actual state of cardiac rehabilitation in Romania by identifying the healthcare facilities that provide and deliver cardiac rehabilitation services. Methods: The research began with a comprehensive investigation into cardiac rehabilitation centers across Romania. This involved leveraging search engines to identify these facilities. Keywords like “cardiac rehabilitation”, “cardiovascular rehabilitation”, and “cardiac rehabilitation centers” were instrumental in pinpointing relevant information, which included names, geographical locations, and contact details of the centers. Upon identification of potential centers, our research team initiated direct engagement with these facilities via telephonic interviews. Results: The data collected in 2024 was compared to previous findings from a 2017 research report to evaluate the progress and impact of prevention efforts over time. While the number of cardiac rehabilitation centers has grown (69.2% increase in the nationwide count of cardiac rehabilitation centers/facilities), an uneven geographic distribution persists, exacerbated by disruptions during the COVID-19 pandemic. Among the cardiac rehabilitation centers identified, 23% are located in balneoclimatic resorts, but the majority of cardiac rehabilitation centers are located in Bucharest. Overall, 65.3% of all identified centers in Romania belong to the private healthcare sector. Among these private centers, 41.1% offer cardiac rehabilitation programs as continuous inpatient care, with durations ranging from 5 to 16 days. All cardiac rehabilitation centers are equipped with the necessary equipment to perform basic cardiological investigations as well as physio-kinesiological rehabilitative procedures, in addition to aerobic physical training (53.8%). In 33.3% of the identified centers, diabetologists and psychologists/psychotherapists are integral members of the multidisciplinary cardiac rehabilitation team, while only 19.2% of the centers include a dietitian/nutritionist. Regarding costs, there is significant variation depending on the geographical area. In Bucharest, a single rehabilitation session costs between 100 to 400 lei (20 to 80 €), and a rehabilitation program spanning 4-6 weeks can cost up to 3350 lei. Comparing costs identified in 2017, we have observed an increase ranging from 47% to 188% in 2024. Conclusions: Despite an increase in the number of cardiac rehabilitation centers, their prevalence remains inadequate to fulfill the demands of the population. Telerehabilitation emerges as a promising solution, with limited adoption in only one center. Cost variations across regions pose a barrier to patient participation. Our article proposes strategies including decision algorithms for personalized recommendations, expanding cardiac rehabilitation centers, and advocating for comprehensive cost reimbursement. The urgent need for collaborative efforts is emphasized, envisioning innovative solutions like mobile applications to foster a sense of community and optimize cardiac rehabilitation, ultimately improving cardiovascular health outcomes in Romania. Keywords: cardiac rehabilitation, telerehabilitation, cardiac rehabilitation centers, healthcare disparities, cardiovascular health

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. This hypothesis-generating analysis used biospecimens collected from a multi-centre 2×2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12weeks of (1) aerobic exercise (moderate intensity titrated to 220min/week); (2) metformin (850mg daily for 2weeks and then titrated to 850mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Randomization to exercise increased leukaemia inhibitory factor (1.26pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P=0.001) and interleukin-15 (2.23pg/mL, 95% CI: 0.87, 3.60; adjusted P=0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69pg/mL, 95% CI: -4.31, -1.07; adjusted P=0.014) and interleukin-15 (-1.74pg/mL, 95% CI: -2.79, -0.69; adjusted P=0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

Multimodality Treatment of Trigeminal Neuralgia: An Institutional Experience.

Object Trigeminal neuralgia (TN) consists of excruciating paroxysmal pain, which lasts for seconds to minutes, in the distribution of fifth cranial nerve. TN is not life-threatening, but life became miserable because of high intensity of pain. This study aimed to assess the overall success rates of different treatments, considering pain relief, recurrence rates, and potential side effects. Material and Methods A total of 203 patients of TN treated in the period of last 10 years, that is, 2013 to 2022, were included. Medial management was in 103, radiofrequency ablation in 17, neurectomy in 9, tumor excision in 6, and microvascular decompression (MVD) was done in 68 patients. Magnetic resonance imaging brain with fast imaging employing steady-state acquisition was the basic investigation to decide the etiology of disease. Results Preliminary findings from our institutional experience indicate that a multidisciplinary approach, combining medical, surgical, and noninvasive treatments, yielded the most favorable results in managing TN. The majority of patients achieved significant pain reduction and improved quality of life with these selected therapies. However, certain subgroups of patients exhibited a higher propensity for treatment resistance, necessitating further investigation into personalized treatment strategies. Conclusion Our study concludes that there is no definitive treatment modality (either medical or surgical) available for patients with TN. As the etiology of TN is varied, management of TN also varied, that is, multidisciplinary approach. Every type of treatment has pros and cons but when the cause of TN is vascular compression and patient's general condition permits for surgery, in such cases MVD should be preferred over the ablative procedures.

Odontogenic cysts in the maxillary sinus: A case series

In this article, we present a series of three patients who reported to the department with different chief complaints. The patients underwent the necessary basic and advanced radiological investigations which showed presence of cysts along with impacted teeth in the maxillary sinus, following which all the patients were subjected to cyst enucleation under GA and the surgical specimens were sent for histopathological examination for definitive diagnosis.

Extracellular vesicles and glycans: new avenue for biomarker research.

The investigation of biomarkers is constantly evolving. New molecules and molecular assemblies, such as soluble and particulate complexes, emerged as biomarkers from basic research and investigation of different proteomes, genomes, and glycomes. Extracellular vesicles (EVs), and glycans, complex carbohydrates are ubiquitous in nature. The composition and structure of both reflect physiological state of paternal cells and are strikingly changed in diseases. The EV-associated glycans, alone or in combination with soluble glycans in related biological fluids, used as analytes, aim to capture full complex biomarker picture, enabling its use in different clinical settings. Bringing together EVs and glycans can help to extract meaningful data from their extreme and distinct heterogeneities for use in the real-time diagnostics. The glycans on the surface of EVs could mark their subpopulations and establish the glycosignature, the solubilisation signature and molecular patterns. They all contribute to a new way of looking at and looking for composite biomarkers.

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5–14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

Striatal Dopamine Contributions to Skilled Motor Learning.

Coordinated multijoint limb and digit movements-"manual dexterity"-underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that corticostriatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release in both male and female mice as they learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In the dorsolateral striatum, dopamine dynamics are faster than in the dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of the striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.

Exploring biological mechanisms in orthodontic tooth movement: Bridging the gap between basic research experiments and clinical applications – A comprehensive review

ObjectivesThe molecular mechanisms behind orthodontic tooth movements (OTM) were investigated by clarifying the role of chemical messengers released by cells. MethodsUsing the Cochrane library, Google scholar, and PubMed databases, a literature search was conducted, and studies published from 1984 to 2024 were considered. ResultsBoth bone growth and remodeling may occur when a tooth is subjected to mechanical stress. These chemicals have a significant effect on the stimulation and regulation of osteoblasts, osteoclasts, and osteocytes during alveolar bone remodeling. This regulation can take place in pathological conditions, such as periodontal diseases, or during OTM alone. This comprehensive review outlines key molecular mechanisms underlying OTM and explores various clinical assumptions associated with specific molecules and their functional domains during this process. Furthermore, clinical applications of certain molecules such as relaxin, prostaglandin E (PGE), and interleukin-1β (IL-1β) in accelerating OTM have been reported. Our findings underscore the existing gap between OTM clinical applications and basic research investigations. ConclusionA comprehensive understanding of orthodontic treatment is enriched by insights into biological systems. We reported the activation of osteoblasts, osteoclast precursor cells, osteoclasts, and osteocytes in response to mechanical stress, leading to targeted cellular and molecular interventions and facilitating rapid and regulated alveolar bone remodeling during tooth movement. Despite the shortcomings of clinical studies in accelerating OTM, this review highlights the crucial role of biological agents in this process and advocates for prioritizing high-quality human studies in future research to gain further insights from clinical trials.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

Consumer Confidence in Digital Finance: Trust Dynamics in Online Banking

Consumer Confidence in Digital Finance: Trust Dynamics in Online Banking

Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD.

A case of primary skeletal muscle lymphoma mimicking cellulitis

Primary skeletal muscle lymphoma is a rare entity. Their presentation can be easily confused with a wide variety of inflammatory conditions, neoplasia as well as infectious diseases. We came across a 65-year-old lady who presented to us with complains of pain and swelling in the right thigh, leg and foot and fever-on and off for 20 days. She was initially managed elsewhere on the line of cellulitis with incision and drainage of right leg 15 days back but there had been no clinical improvement. We took her detailed history and examined her thoroughly. Relevant blood investigations were sent. However, the clinical examination findings and history were suggestive of an infective cause, blood investigations were suggestive of an acute inflammatory pathology, whereas radiological investigations (NCCT and X-ray) and cytological investigations (FNAC) which were performed at the previous place of treatment were inconclusive. We then did a CE-MRI of the right lower limb which showed centrally necrotic, enhancing mass lesion involving peroneal muscles with multiple enlarged inguinal and popliteal lymph nodes. Based on this finding, biopsy was performed and specimen was sent for histopathological examination which revealed “malignant small round cell tumor”. Immunohistochemistry was then done and tumor cells were found to be positive for vimentin, LCA, CD20 and negative for PANCK and CD3. Based on the above findings it was diagnosed as “non-hodgkin’s lymphoma (NHL) B-cell type” of right leg. Considering the confusing clinical presentation of this entity and inconclusiveness of blood and basic radiological investigations, lesions of extremities presenting with features of cellulitis must be carefully assessed.