Cortical sites critical to language function act as connectors between language subnetworks.

Historically, eloquent functions have been viewed as localized to focal areas of human cerebral cortex, while more recent studies suggest they are encoded by distributed networks. We examined the network properties of cortical sites defined by stimulation to be critical for speech and language, using electrocorticography from sixteen participants during word-reading. We discovered distinct network signatures for sites where stimulation caused speech arrest and language errors. Both demonstrated lower local and global connectivity, whereas sites causing language errors exhibited higher inter-community connectivity, identifying them as connectors between modules in the language network. We used machine learning to classify these site types with reasonably high accuracy, even across participants, suggesting that a site's pattern of connections within the task-activated language network helps determine its importance to function. These findings help to bridge the gap in our understanding of how focal cortical stimulation interacts with complex brain networks to elicit language deficits.

A Study of Community-Acquired Pyodermas with Special Reference to Panton-Valentine Leukocidin (PVL)-Positive Methicillin-Resistant Staphylococcus Aureus.

Background: Community-acquired (CA) pyodermas are one of the most common infections encountered in the dermatology outpatient clinics. A significant number of these conditions are caused by Staphylococcus aureus. CA-methicillin-sensitive Staphylococcus aureus (MSSA) and CA-methicillin-resistant Staphylococcus aureus (MRSA) have specific virulence genes which are associated with these diseases, particularly the Panton-Valentine leukocidin (PVL) genes. The presence of the PVL gene as a virulence factor may be associated with recurrent and severe skin infections. Materials and Methods: A prospective study was conducted with 205 cases of CA pyodermas, of which five were discarded due to mixed isolates. Clinical details were taken and wound exudate was sent for bacteriological examination. Further, the molecular study was performed on all MRSA (7) isolates and 13 randomly selected MSSA isolates using polymerase chain reaction for mecA and PVL genes. Results: Staphylococcus aureus was the most common organism (90%) isolated from primary or secondary CA pyodermas. The prevalence of CA-MRSA among all pyodermas was 3.5% in our community. The PVL gene was not detected in all tested CA-MRSA and CA-MSSA isolates. Conclusion: While pyodermas are common, the prevalence of MRSA is low in the CA pyodermas in our region. PVL does not appear to be a virulence factor among the isolated MRSA. Larger, multicentric, and periodic studies are, however, required to further justify these claims.

Epidermolysis bullosa in a mother-infant dyad.

Epidermolysis Bullosa is an inherited mechanobullous disorder which presents in the neonatal period as blistering skin lesions. In this case report, we describe an uncommon presentation of Epidermolysis Bullosa Simplex in a term infant, weighing 2640 g, born to a mother who was also diagnosed with Epidermolysis Bullosa Pruriginosa during the course of the evaluation of her newborn. The clinical situation presented us with a unique dilemma with regard to routine newborn care practices including handling, skin and diaper care. Though the presentation was typically characteristic of EB, we illustrate with images the diagnostic modalities and challenges faced in the hospital while caring for this fragile skin in a low and middle-income country's neonatal intensive care unit. This is the first reported case of a neonate with Epidermolysis Bullosa Simplex born to a mother with Epidermolysis Bullosa Pruriginosa.

Revascularisation Options for Chronic Limb Threatening Ischaemia in Diabetes: Implications From Two Recent Trials.

Chronic limb-threatening ischaemia (CLTI) is a severe form of peripheral arterial disease (PAD) and is associated with an increased risk of amputation, mortality, and significantly impaired quality of life. International guidelines recommend considering timely revascularisation and optimal medical therapy to improve limb perfusion in individuals with CLTI. The 2 primary revascularization approaches for CLTI are open bypass surgery (BS) and endovascular therapy (EV), however, there is currently no consensus on the best initial treatment strategy for CLTI, leading to uncertainty among clinicians. To shed light on this issue, 2 recent trials, namely best endovascular versus best surgical therapy in patients with CLI (BEST-CLI) and bypass versus angioplasty for severe ischaemia of the leg (BASIL-2), have tried to provide valuable insights. While a definitive conclusion on the optimal revascularisation approach is still pending, these trials offer immediate and clinically relevant information to the diabetic foot multidisciplinary team. The trials encompassed a distinct range of patient cohorts and included participants with varying degrees of medical and physical frailty. Taken together, their findings, highlight the need for an individualised revascularisation strategy which accounts for underlying comorbidities, risk factors, disease severity, availability of suitable bypass conduits, surgical risks, and timely access to procedures. Regardless of the chosen strategy, early referral of patients with diabetes and CLTI to a specialist team within a multidisciplinary environment is crucial. Comprehensive care should encompass essential elements such as adequate debridement, infection control, offloading, glycaemic control, smoking cessation, and patient education. By addressing these aspects, healthcare providers can optimise the management and outcomes for individuals with CLTI and diabetes.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy. However, additional testing showed reduced sweat gland function most likely related to degeneration of c-fibres (small fibre neuropathy). This case raises the awareness that in addition to the "textbook" description, in diabetes, Charcot foot can develop in individuals with "minimal" or "no signs" of clinical neuropathy. The onset of active Charcot foot should be suspected in every person with diabetes and history of trauma even when foot and ankle x-rays are normal. Offloading should be initiated until the diagnosis is proven otherwise.

Outcomes after Emergency Admission with a Diabetic Foot Attack Indicate a High Rate of Healing and Limb Salvage But Increased Mortality: 18-Month Follow-up Study.

AIM: The diabetic foot attack (DFA) is perhaps the most devastating form of diabetic foot infection, presenting with rapidly progressive skin and tissue necrosis, threatening both limb and life. However, clinical outcome data in this specific group of patients are not available. METHODS: Analysis of 106 consecutive patients who underwent emergency hospitalisation for DFA (TEXAS Grade 3B or 3D and Infectious Diseases Society of America (IDSA) Class 4 criteria). Outcomes evaluated were: 1) Healing 2) major amputation 3) death 4) not healed. The first outcome reached in one of these four categories over the follow-up period (18.4±3.6 months) was considered. We also estimated amputation free survival. RESULTS: Overall, 57.5% (n=61) healed, 5.6% (n=6) underwent major amputation, 23.5% (n=25) died without healing and 13.2% (n=14) were alive without healing. Predictive factors associated with outcomes were: Healing (age<60, p=0.0017; no Peripheral arterial disease (PAD) p= 0.002; not on dialysis p=0.006); major amputation (CRP>100 mg/L, p=0.001; gram+ve organisms, p=0.0013; dialysis, p= 0.001), and for death (age>60, p= 0.0001; gram+ve organisms p=0.004; presence of PAD, p=0.0032; CRP, p=0.034). The major amputation free survival was 71% during the first 12 months from admission, however it had reduced to 55.4% by the end of the follow-up period. CONCLUSIONS: In a unique population of hospitalised individuals with DFA, we report excellent healing and limb salvage rates using a dedicated protocol in a multidisciplinary setting. An additional novel finding was the concerning observation that such an admission was associated with high 18-month mortality, almost all of which was after discharge from hospital.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.

People living with diabetes are unaware of their foot risk status or why they are referred to a multidisciplinary foot team.

AIM: People with active diabetic foot disease should be rapidly referred by health professionals along a pathway of care to a multidisciplinary foot team. The aim was to investigate patients' self-reported understanding of their foot risk status and reasons for their referral to a multidisciplinary foot team. METHOD: This seven-month service evaluation included consecutive newly referred patients. Participants completed a questionnaire which asked firstly about their understanding of their foot risk status, secondly about their pathway of care before presentation to the multidisciplinary foot team, and thirdly about their interest in diabetes-related foot education and preferred learning style. RESULTS: There were 202 participants; 65% were male, mean age was 64±15 years (mean±standard deviation (SD)), 86% had type 2 diabetes, and mean HbA1c was 65±23mmol/mol (8.3±3.7%). Only 4% of participants knew their current foot risk status and 52% did not know why their care had been escalated to a multidisciplinary foot clinic. Participants with type 2 diabetes more readily expressed an interest in further foot education compared with participants with type 1 diabetes, (70% versus 29%, p=0.001). CONCLUSIONS: These findings show that people with diabetes and foot disease are less aware of their foot risk status or why they are referred to a multidisciplinary team. Participants indicated a variable interest in further learning about foot complications. These findings indicate possible communication and educational barriers between patients and health professionals which may contribute to delayed presentation or suboptimal engagement.

Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

Diabetic Peripheral Neuropathy and Depression: Dancing with Wolves? - Mini-Review and Commentary on Alghafri et al. "Screening for depressive symptoms amongst patients with diabetic peripheral neuropathy".

The co-existence of diabetic peripheral neuropathy (DPN) and depression in subjects with diabetes is being increasingly recognized. The interaction of these two serious comorbidities may increase morbidity and mortality. An emerging thought is that persisting depression, along with stroke and cognitive dysfunction, may represent a cluster of potential microvascular injuries affecting the brain, which shares a common risk factor with DPN. Current evidence highlights metabolic and clinical covariates, which may interact in subjects with DPN and depression. However, there is a lack of rigorous enquiry into the confounding effect of cognitive dysfunction and vascular brain disease. Furthermore, high-quality longitudinal studies exploring the direct impact of these comorbidities on diabetes course and on the progression of the comorbidities themselves are lacking. Improved insights into comorbid DPN and depression may help to improve screening for and treatment of both these conditions.

Isolated low toe-brachial index is associated with increased mortality and morbidity: a retrospective cohort study.

OBJECTIVE: The aim was to assess the prognostic impact of perfusion assessments including ankle-brachial Index (ABI) and toe-brachial Index (TBI) on survival of patients who present with diabetic foot ulceration and to analyse clinical outcomes when patients are categorised into three levels of limb ischaemia. METHOD: This was a retrospective cohort analysis of consecutive patients presenting with foot ulceration. Patients continued with their standard of care, after having baseline assessments of limb perfusion. Patients were retrospectively categorised into three groups according to baseline ABI and TBI: Group 1 (n=31) non-ischaemic (TBI≥0.75, ABI≥0.9), Group 2 (n=67) isolated low TBI with foot ischaemia (TBI<0.75, ABI≥0.90) and Group 3 (n=30) foot-leg ischaemia (TBI<0.75, ABI<0.90). RESULTS: A total of 128 patients took part in the study. Low TBI was associated with a significant decrease in patient survival (42±20 versus 51±16 months, p=0.011). There was a progressive and significant decline in mean patient survival time (51±16 versus 44±20 versus 39±22 months, respectively, for ANOVA across the three groups, p=0.04). Patients with isolated low TBI had angioplasty and bypass at a rate similar to that of patients in Group 3 (low ABI and low TBI). The proportion of angioplasties was significantly higher in the isolated low TBI (19.4% (13/67) versus the non-ischaemic 3.2% (1/31), p=0.033). Such revascularisation resulted in ulcer healing within the foot ischaemic group that was similar to the non-ischaemic group (68% versus 60% over 12 months, p=0.454). CONCLUSION: Regardless of ABI level, measurement of TBI identifies patients with isolated low TBI who require specialised care pathways and revascularisation to achieve ulcer healing that is similar to non-ischaemic patients.

Admission Time Deep Swab Specimens Compared With Surgical Bone Sampling in Hospitalized Individuals With Diabetic Foot Osteomyelitis and Soft Tissue Infection.

Whether deep swab cultures taken at admission reliably identify pathogens compared to surgical bone specimens in hospitalized individuals with diabetic foot osteomyelitis and soft tissue infection is unclear. Comparison of microbiological isolates between a deep wound swab (DWS) taken at the time of admission through the actively infected, discharging ulcer probing to the bone and the subsequent surgical bone sample (SBS) taken during surgical debridement was made. A total of 63 subjects (age 60.8 ± 13.5 years, 75% male, 80% Type 2 diabetes, HbA1C 8.9%±2.2%) were included. The proportion of Gram-positive (DWS 49% v SBS 52%) and Gram-negative (DWS 60% v SBS 60%) isolates was similar between the techniques. However, the overall concordance of isolates between the two techniques was only fair (κ=0.302). The best concordance was observed for Staphylococcus aureus (κ=0.571) and MRSA (κ=0.644). There was a correlation between number of isolates in SBS with prior antibiotic therapy of any duration (r= -0.358, p=0.005) and with the duration of ulceration (r=0.296, p=0.045); no clinical correlations were found for DWS. Prior antibiotic therapy (p=0.03) and duration of ulceration <8 weeks (p=0.025) were predictive of negative growth on SBS. In conclusion, we found only a fair concordance between deep wound swabs acquired at admission and surgical bone specimens in those presenting with a severe diabetic foot infection and features of osteomyelitis. Ensuring early surgical debridement of all infected tissue and obtaining bone specimens should be considered a clinical priority, which may also reduce the likelihood of negative growth on SBS.

Pharmacological Treatments for Diabetic Foot Disease: Current State and Future Perspectives.

The care of the individual with diabetic foot disease (DFD) represents a significant challenge. In addition to the primary foot pathology, individuals with DFD are frequently compromised by multiple co-existent medical complications. Successful management of DFD, therefore requires simultaneous addressal of these issues alongside high-quality foot care. We explore the pharmacological treatments in DFD with an emphasis on the emerging putative technologies centred on addressing the pathobiology of wound healing but also discuss developments in infection control, Charcot neuroarthropathy, cardiovascular and diabetes care. Many of these will have a significant impact on future treatment paradigms and how we amalgamate these novel technologies may help shape the standard of care in DFD hereafter. However, there is a need for better quality of evidence and cost-effectiveness data prior to widespread adoption into routine care is considered.

Ultrasound Devices to Treat Chronic Wounds: The Current Level of Evidence.

Chronic wounds cause considerable morbidity and utilize significant health care resources. In addition to addressing wound etiology and treating infection, regular debridement is a key component of wound care with a proven ability to accelerate healing. In this regard, a significant innovation in wound care has been the development of ultrasound debridement technology. The purpose of this review is to evaluate the current evidence behind the technology with an emphasis on noncontact low-frequency (NCLF) ultrasound. A number of studies, especially those evaluating NCLF technology, have demonstrated the potential of ultrasound debridement to effectively remove devitalized tissue, control bioburden, alleviate pain, and expedite healing. However, most of the studies are underpowered, involve heterogeneous ulcer types, and demonstrate significant methodological limitations making comparison between studies difficult; there is a paucity of data on cost-effectiveness. Future clinical trials on ultrasound debridement technology must address the design issues prevalent in current studies, and report on clinically relevant endpoints before adoption into best-practice algorithms can be recommended.

River basin salinization as a form of aridity.

Soil-salinization affects, to a different extent, more than one-third of terrestrial river basins (estimate based on the Food and Agriculture Organization Harmonized World Soil Database, 2012). Among these, many are endorheic and ephemeral systems already encompassing different degrees of aridity, land degradation, and vulnerability to climate change. The primary effect of salinization is to limit plant water uptake and evapotranspiration, thereby reducing available soil moisture and impairing soil fertility. In this, salinization resembles aridity and-similarly to aridity-may impose significant controls on hydrological partitioning and the strength of land-vegetation-atmosphere interactions at the catchment scale. However, the long-term impacts of salinization on the terrestrial water balance are still largely unquantified. Here, we introduce a modified Budyko's framework explicitly accounting for catchment-scale salinization and species-specific plant salt tolerance. The proposed framework is used to interpret the water-budget data of 237 Australian catchments-29% of which are already severely salt-affected-from the Australian Water Availability Project (AWAP). Our results provide theoretical and experimental evidence that salinization does influence the hydrological partitioning of salt-affected watersheds, imposing significant constraints on water availability and enhancing aridity. The same approach can be applied to estimate salinization level and vegetation salt tolerance at the basin scale, which would be difficult to assess through classical observational techniques. We also demonstrate that plant salt tolerance has a preeminent role in regulating the feedback of vegetation on the soil water budget of salt-affected basins.

Charcot foot reconstruction outcomes: A systematic review.

BACKGROUND: Charcot neuroarthropathy is a complex condition characterised by progressive deformity, limited treatment options and a high amputation rate. Surgical reconstruction of Charcot foot has been proposed as a method to preserve the foot. However, limited information exists on the different methods of reconstruction available, their outcomes and complications. METHODS: We systematically analysed published data from Jan 1993 to Dec 2018 to assess methods of fixation and associated outcomes for the surgical reconstruction in Charcot neuroarthropathy. Statistical analyses were undertaken to determine the amputation rates, return to ambulation and complications associated with these techniques. RESULTS: A total of 1116 feet (1089 patients) were reported to have undergone reconstruction with significant heterogeneity in patient selection. Of these, 726 (65%) were reported to undergo internal fixation, 346 feet (31%) external fixation and 44 (4%) undergoing simultaneous internal and external fixation. No single technique demonstrated a significant benefit over the other. Overall, the bone fusion rate was 86.1%. Complications directly attributable to the technique employed were noted in 36% of individuals. The reported post-reconstruction amputation rate was only 5.5% with 91% apparently returning to ambulation. CONCLUSIONS: Although no preferential method of fixation was identified, we find that the current options for surgical reconstruction could offer limb salvage with a low amputation risk in a highly selected population. However, the lack of controlled studies, inconsistent reporting of outcomes and heterogeneity of patient selection mean that the quality of evidence is low.