Precision Genome Editing Techniques in Gene Therapy: Current State and Future Prospects.

Precision genome editing is a rapidly evolving field in gene therapy, allowing for the precise modification of genetic material. The CRISPR and Cas systems, particularly the CRISPRCas9 system, have revolutionized genetic research and therapeutic development by enabling precise changes like single-nucleotide substitutions, insertions, and deletions. This technology has the potential to correct disease-causing mutations at their source, allowing for the treatment of various genetic diseases. Programmable nucleases like CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), and zinc finger nucleases (ZFNs) can be used to restore normal gene function, paving the way for novel therapeutic interventions. However, challenges, such as off-target effects, unintended modifications, and ethical concerns surrounding germline editing, require careful consideration and mitigation strategies. Researchers are exploring innovative solutions, such as enhanced nucleases, refined delivery methods, and improved bioinformatics tools for predicting and minimizing off-target effects. The prospects of precision genome editing in gene therapy are promising, with continued research and innovation expected to refine existing techniques and uncover new therapeutic applications.

Charcot neuroarthropathy of the foot and ankle: a review.

Charcot neuroarthropathy is a limb-threatening, destructive process that occurs in patients with neuropathy associated with medical diseases such as diabetes mellitus. Clinicians' treating diabetic patients should be vigilant in recognizing the early signs of acute Charcot neuroarthropathy, such as pain, warmth, edema, or pathologic fracture in a neuropathic foot. Early detection and prompt treatment can prevent joint and bone destruction, which, if untreated, can lead to morbidity and high-level amputation. A high degree of suspicion is necessary. Once the early signs have been detected, prompt immobilization and offloading are important. Treatment should be determined on an individual basis, and it must be determined whether a patient can be treated conservatively or will require surgical intervention when entering the chronic phase. If diagnosed early, medical and conservative measures only will be required. Surgery is indicated for patients with severe or unstable deformities that, if untreated, will result in major amputations. A team approach that includes a foot and ankle surgeon, a diabetologist, a physiotherapist, a medical social councilor, and, most importantly, the patient and immediate family members is vital for successful management of this serious condition.

Foot care practice - the key to prevent diabetic foot ulcers in India.

BACKGROUND: The magnitude of diabetic foot ulcers (DFUs) and the amputation rates due to DFUs remain high even in developing and developed countries. Yet, the influence of knowledge, attitude, and practice (KAP) of diabetic foot care (DFC) on DFU incidence is not studied much. OBJECTIVE: To study causal relationship between knowledge, attitude and practice (KAP) on DFC between diabetic patients with and without DFUs; and the risk factors associated with DFUs. METHODS: A consecutive of 203 diabetic patients (103 with DFU and 100 without DFU) were included in the study. Their demographic details, medical history, and personal habits were recorded. KAP on DFC was assessed using a questionnaire. Responses were recorded, scored, and analyzed. RESULTS: Of the cohort, 67.5% were males, mean age: 59.9 ± 11.4 years. Patients without DFU had good knowledge on DFC compared to those with DFU (86% versus 69.9%) (p<0.001). Incidence of DFU was 9% and 39.8% (p<0.001) among patients who practiced and not practiced DFC respectively. 88% patients with and without DFUs; showed favorable attitude toward adopting DFC. Risk factors - diabetic peripheral neuropathy, peripheral vascular disease, retinopathy, nephropathy, smoking, tobacco chewing and alcohol consumption were significantly (p<0.001) associated with DFUs. CONCLUSIONS: An inverse relationship between DFU and foot care knowledge as well as practice was observed. Apart from tight glycemic control, diabetic patients must be educated and motivated on proper foot care practice and life style modifications for preventing DFUs.

Reconstructive foot and ankle surgeries in diabetic patients.

Diabetic foot and ankle deformities are secondary to long-standing diabetes and neglected foot care. The concept of surgical correction for these deformities is quite recent. The primary objective of reconstructive foot and ankle surgery is the reduction of increased plantar pressures, reduction of pain and the restoration of function, stability and proper appearance. Foot and ankle deformities can result in significant disability, loss of life style, employment and even the loss of the lower limb. Therefore, restoration of normal, problem free foot function and activities will have a significant impact on peoples' lives. Reconstructive surgical procedures are complex and during reconstruction, internal and external fixation devices, including pins, compression screws, staples, and wires, may be used for repair and stabilization. The surgeries performed depend on the type and severity of the condition. Surgery can involve any part of the foot and ankle, and may involve tendon, bone, joint, tissue or skin repair. Corrective surgeries can at times be performed on an outpatient basis with minimally invasive techniques. Recovery time depends on the type of condition being treated.

Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes.

The prevalence rate and spectrum of fungi infecting deep tissues of diabetic lower-limb wounds (DLWs) have not been previously studied. Five hundred eighteen (382 male and 136 female) consecutive patients with type 2 diabetes hospitalized due to infected lower-limb wounds were enlisted in this study. Deep tissue (approximately 0.5- x 0.5-cm size) taken perioperatively from the wound bed was cultured for fungi. Fungi was found in 27.2% (141/518) of the study population. Candida parapsilosis (25.5%), Candida tropicalis (22.7%), Trichosporon asahii (12.8%), Candida albicans (10.6%), and Aspergillus species (5.0%) were the most predominant fungal isolates. Of the fungal isolates, 17.7% were resistant to itraconazole, 6.9% were resistant to amphotericin B, 6.9% were resistant to voriconazole, 3.9% were resistant to fluconazole, and 1.5% were resistant to flucytosine. Of the population, 79.7% (413/518) had bacterial infection in deep tissue. The predominant isolates were Enterococcus faecalis (14.1%), Staphylococcus aureus (12.2%), and Pseudomonas aeruginosa (10.8%). Mixed fungal and bacterial infections were seen in 21.4% of patients, while 5.8% had only fungal infection and 58.3% had only bacterial infections. Another 14.5% had neither bacteria nor fungi in the deep tissue. Patients with higher glycosylated hemoglobin levels had significantly more fungal infections. Our study reveals that deep-seated fungal infections are high in DLWs. In the context of delayed wound healing and amputation rates due to DLWs, it is important to study the pathogenicity of fungi in deep tissues of DLWs and their possible contribution to delayed wound healing. The role of antifungal agents in wound management needs to be evaluated further.

Tropical chronic pancreatitis and peripheral vascular disease. A case report.

CONTEXT: It is well-known that subjects with diabetes resulting from tropical chronic pancreatitis are prone to diabetic microvascular complications (neuropathy, nephropathy and retinopathy). However, macrovascular complications (coronary artery disease, stroke and peripheral vessel disease) are rare, as these subjects are younger, leaner and have lower cholesterol levels. CASE REPORT: We report the case of a 51-year-old male who had tropical chronic pancreatitis, diabetes and severe peripheral vessel disease with gangrene. He was lean, had borderline lipid levels and was normotensive. His ECG was normal. CONCLUSIONS: Peripheral vascular disease can occur in these diabetic subjects, even without additional risk factors for atherosclerotic vascular disease. All subjects with tropical chronic pancreatitis and diabetes should have a complete foot examination once a year, in addition to screening for other vascular complications.