Author Response: The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study.

How to cite this article: Tiwari AM, Zirpe KG, Kulkarni AP. Author Response: The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) During Resuscitation Affects ICU Outcomes: A Prospective Observational Study. Indian J Crit Care Med 2024;28(7):710.

Hypoeutectic Liquid Metal Printing of 2D Indium Gallium Oxide Transistors.

2D native surface oxides formed on low melting temperature metals such as indium and gallium offer unique opportunities for fabricating high-performance flexible electronics and optoelectronics based on a new class of liquid metal printing (LMP). An inherent property of these Cabrera-Mott 2D oxides is their suboxide nature (e.g., In2O3-x), which leads high mobility LMP semiconductors to exhibit high electron concentrations (ne > 1019 cm-3) limiting electrostatic control. Binary alloying of the molten precursor can produce doped, ternary metal oxides such as In-X-O with enhanced electronic performance and greater bias-stress stability, though this approach demands a deeper understanding of the native oxides of alloys. This work presents an approach for hypoeutectic rapid LMP of crystalline InGaOx (IGO) at ultralow process temperatures (180 °C) beyond the state of the art to fabricate transistors with 10X steeper subthreshold slope and high mobility (≈18 cm2 Vs-1). Detailed characterization of IGO crystallinity, composition, and morphology, as well as measurements of its electronic density of states (DOS), show the impact of Ga-doping and reveal the limits of doping induced amorphization from hypoeutectic precursors. The ultralow process temperatures and compatibility with high-k Al2O3 dielectrics shown here indicate potential for 2D IGO to drive low-power flexible transparent electronics.

Parkinson's Disease and Mitotherapy-Based Approaches towards α-Synucleinopathies.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain and the formation of intracellular protein aggregates known as Lewy bodies, of which a major component is the protein α-synuclein. Several studies have suggested that mitochondria play a central role in the pathogenesis of PD, encompassing both familial and sporadic forms of the disease. Mitochondrial dysfunction is attributed to bioenergetic impairment, increased oxidative stress, damage to mitochondrial DNA, and alteration in mitochondrial morphology. These alterations may contribute to improper functioning of the central nervous system and ultimately lead to neurodegeneration. The perturbation of mitochondrial function makes it a potential target, worthy of exploration for neuroprotective therapies and to improve mitochondrial health in PD. Thus, in the current review, we provide an update on mitochondria-based therapeutic approaches toward α-synucleinopathies in PD.

Drug repurposing for cancer.

In the dynamic landscape of cancer therapeutics, the innovative strategy of drug repurposing emerges as a transformative paradigm, heralding a new era in the fight against malignancies. This book chapter aims to embark on the comprehension of the strategic deployment of approved drugs for repurposing and the meticulous journey of drug repurposing from earlier times to the current era. Moreover, the chapter underscores the multifaceted and complex nature of cancer biology, and the evolving field of cancer drug therapeutics while emphasizing the mandate of drug repurposing to advance cancer therapeutics. Importantly, the narrative explores the latest tools, technologies, and cutting-edge methodologies including high-throughput screening, omics technologies, and artificial intelligence-driven approaches, for shaping and accelerating the pace of drug repurposing to uncover novel cancer therapeutic avenues. The chapter critically assesses the breakthroughs, expanding the repertoire of repurposing drug candidates in cancer, and their major categories. Another focal point of this book chapter is that it addresses the emergence of combination therapies involving repurposed drugs, reflecting a shift towards personalized and synergistic treatment approaches. The expert analysis delves into the intricacies of combinatorial regimens, elucidating their potential to target heterogeneous cancer populations and overcome resistance mechanisms, thereby enhancing treatment efficacy. Therefore, this chapter provides in-depth insights into the potential of repurposing towards bringing the much-needed big leap in the field of cancer therapeutics.

Drug repurposing for neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.

To Access Knowledge Regarding Organ Donation among Healthcare Workers and Their Willingness toward Organ Donation.

BACKGROUND: In India, critical shortage of organ donations, particularly deceased donations, has led to a dire situation in India, with thousands of patients waiting for transplants and a significant number of them succumbing. One of the reasons for the shortage of organs for transplantation is unawareness and prejudiced information about organ donation. Being direct or indirect stakeholders, the knowledge regarding organ donation among healthcare workers may play an important role in the donation process. AIM: To assess the knowledge regarding cadaver organ donation among healthcare workers and their willingness toward organ donation. MATERIALS AND METHODS: It is a cross-sectional offline self-administered questionnaire-based survey conducted among healthcare professionals at tertiary care teaching institutes. Survey was carried out between the months of August to December 2019. A structured questionnaire was used to assess knowledge and willingness toward organ donation. Statistical analyzed was done by using statistical package for social sciences (SPSS) 20.0. All p-values were considered significant at <0.05. RESULTS: A total of 1,039 healthcare professionals participated in the survey. Out of them, 362 (34.8%) were males and 675 (65%) were females. Average age of the healthcare workers participating in survey was 30.81 years, and age ranged from 18 to 60 years. Awareness regarding corneal donation after brain death was found to be maximum (89.7%) and was comparable to that of kidney (86.6%) and heart (83.7%). Participants were unlearned of donation of lungs, pancreas, hands and unaware of heart valve donation. About 45% respondents considered that age affected the donors. About 40% respondents considered younger patients as ideal recipients, while 18.7% respondents considered waiting list patients as ideal recipients. Doctors had highest willingness (78. 3%) for organ donation, followed by nurses (69.9%) and support staff (59.3%) (p < 0.001). Only 119 (11.5%) participants received organ donation cards as against 68.7% willingness toward organ donation (p < 0.01). CONCLUSION: We have observed fair awareness regarding overall cadaver organ donation concept among healthcare workers. There is a need to improve knowledge of extended age criteria and which organs can be retrieved from deceased donor. Authorities have to work hard on delivery of organ donation pledging card to promote donation program.

The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study.

Introduction: The usual methods of perfusion assessment in patients with shock, such as capillary refill time, skin mottling, and serial serum lactate measurements have many limitations. Veno-arterial difference in the partial pressure of carbon dioxide (PCO2 gap) is advocated being more reliable. We evaluated serial change in PCO2 gap during resuscitation in circulatory shock and its effect on ICU outcomes. Materials and methods: This prospective observational study included 110 adults with circulatory shock. Patients were resuscitated as per current standards of care. We recorded invasive arterial pressure, urine output, cardiac index (CI), PCO2 gap at ICU admission at 6, 12, and 24 hours, and various patient outcomes. Results: Significant decrease in PCO2 gap was observed at 6 h and was accompanied by improvement in serum lactate, mean arterial pressure, CI and urine output in (n = 61). We compared these patients with those in whom this decrease did not occur (n = 49). Mortality and ICU LOS was significantly lower in patients with low PCO2 gap, while more patients with high PCO2 gap required RRT. Conclusion: We found that a persistently high PCO2 gap at 6 and 12 h following resuscitation in patients with shock of various etiologies, was associated with increased mortality, need for RRT and increased ICU LOS. High PCO2 gap had a moderate discriminative ability to predict mortality. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Vaidya HS, Gurav SK, Deshmukh AM, et al. The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study. Indian J Crit Care Med 2024;28(4):349-354.

Impact of an Antimicrobial Stewardship Program on Broad Spectrum Antibiotics Consumption in the Intensive Care Setting.

Background and objectives: Antibiotics are the most commonly exploited agents in intensive care units. An antimicrobial stewardship program (ASP) helps in the optimal utilization of antibiotics and prevents the development of antibiotic resistance. The aim of this study was to assess the impact of ASP on broad-spectrum antibiotic consumption in terms of defined daily dose (DDD) and days of therapy (DOT) before and after the implementation of an ASP. Materials and methods: It was a prospective, quasi-experimental, pre- and post-study. Group A consisted of 5 months of ASP data, ASP activities were implemented during the next 2 months and continued. Group B (post-ASP) data was collected for the next 5 months. Total and individual DDDs and DOTs of broad-spectrum antibiotics utilized were compared between group A and group B. Results: Total DDDs used per 100 patient bed days were reduced by 18.72% post-ASP implementation (103.46 to 84.09 grams). The total DOT per 100 patient bed days used was 90.91 vs 71.25 days (21.62% reduction). As per the WHO classification of antibiotics use, the watch category (43.4% vs 43.04%) as well as reserve category (56.6% vs 56.97%) used between the two groups were found similar. The average length of stay (8.9 ± 2 days) after ASP was found significantly lesser than baseline (10.8 ± 3.4 days) (p < 0.05), however, there was no significant change in mortality between the two groups. Conclusion: Antimicrobial stewardship program implementation may reduce overall antibiotic consumption both in terms of DDD and DOT. How to cite this article: Zirpe KG, Kapse US, Gurav SK, Tiwari AM, Deshmukh AM, Suryawanshi PB, et al. Impact of an Antimicrobial Stewardship Program on Broad Spectrum Antibiotics Consumption in the Intensive Care Setting. Indian J Crit Care Med 2023;27(10):737-742.

Evidence of Size Stratification in Colloidal Glass Microgranules Realized by Rapid Evaporative Assembly.

Evaporation is a ubiquitous phenomenon. Rapid evaporation of the continuous phase from micrometric colloidal droplets can be used to realize nanostructured microgranules, constituting the assembled nanoparticles. One of the important aspects of such nonequilibrium assembly is the nature of the packing of nanoparticles in the microgranules. The present work demonstrates the evidence of size stratification of the nanoparticles in such far-from-equilibrium configurations. Small-angle X-ray scattering, in combination with particle packing simulation, reveals the "large on top"-type stratification in such assembled microgranules, where the larger particles get concentrated at the outer shell of the granules while the smaller particles reside in the core region. It also reveals the presence of local clusters in such a rapid evaporative assembly in aerosolized colloidal droplets.

Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study).

Background: Critically ill patients are frequently transported to various locations within the hospital for diagnostic and therapeutic purposes, which increases the risk of adverse events (AEs). This multicenter prospective observational study was undertaken to determine the incidence of AEs related to intrahospital transport, their severity, and their effects on patient outcomes. Patients and methods: We included consecutive unstable critically ill patients requiring intrahospital transport, across 15 Indian tertiary care centers over 5 months (October 11, 2022-February 20, 2023). Apart from the demographics and severity of illness, data related to transport itself, such as indications and destination, incidence of AEs, their category and treatment required, and patient outcomes, were recorded in a standard form. Results: Eight hundred and ninety-three patients were transported on 1065 occasions out of the intensive care unit (ICU). The mean (SD) acute physiology and chronic health evaluation II score of the patients was 15.38 (±7.35). One hundred and two AEs occurred, wherein cardiovascular instability was the most common occurrence (31, 30.4%). Two patients had cardiac arrest immediately after transport. Acute physiology and chronic health evaluation II [odds ratio (OR): 1.02, 95% confidence interval (CI) - 1.00-1.05, p = 0.04], emergent transport (OR: 5.11, 95% CI - 3.32-7.88, p = 0.00), and team composition (OR: 5.34, 95% CI - 1.63-17.5, p = 0.00) during transport were found to be independent predictors of AEs. Conclusion: We found a high incidence of AEs during intrahospital transport of critically ill patients. These events were more common during emergent transports and when the patients were transported by doctors. Transport by itself was not related to ICU mortality. We feel that stabilization of the patients before transport and adherence to a standardized protocol may help in minimizing the AEs, thereby enhancing patient safety. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Govil D, Dixit SB, Munjal M, et al. Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study). Indian J Crit Care Med 2023;27(9):635-641.

Utility of Bedside Ultrasound Measurement of Optic Nerve Sheath Diameter as a Screening Tool for raised Intracranial Pressure in Neurocritical Care Prospective Observational Study.

Intracranial pressure (ICP) needs to be monitored in neurocritical patients. There is a need for portable bedside optic nerve ultrasound (ONUS) for early diagnosis to initiate the measures to reduce ICP Objective: To find the utility of bedside ONUS to diagnose raised ICP in neurocritical care. Materials and methods: After approval from the ethical committee, a prospective observational study was conducted. Optic nerve sheath diameter (ONSD) was measured in two groups: control group patients with neurological symptoms but computed tomography (CT)/magnetic resonance imaging (MRI) not suggestive of raised ICP, and second was study group patients with neurological symptoms and CT/MRI suggestive of elevated ICP Result: In patients with normal ICP, the mean ONSD in females was 4.47mm, and in males was 4.66mm. In patients with raised ICP, the mean ONSD in females was 6.45 ± 0.78 mm, and in males was 6.33 ± 0.70 mm. Regarding the correlation between Glasgow coma scale (GCS) and mean ONSD parameters, the coefficient of correlation (R) is 0.14; thus, there is a weak negative correlation. In our study, no difference was observed in raised mean ONSD in patients with different diagnoses. At a cut-off value of >4.8 mm, the sensitivity and specificity are 100% to diagnose raised ICP. Conclusion: Optic nerve sheath diameter (ONSD) is a reliable, rapid bedside screening tool in the Emergency Department/Critical Care/Operation Theatre to diagnose raised ICP. In order to keep a record of trends in ICP, we need to measure ONSD frequently. There was no correlation between GCS and ONSD measurement.

Epigenetic regulons in Alzheimer's disease.

Alzheimer's disease is one of the most prevalent forms of dementia that occur genetically or sporadically (with increasing age) in the population of 65 years and above. The pathological hallmarks of AD include the formation of extracellular senile plaques of amyloid beta peptides 42 (Aß42) and intracellular neurofibrillary tangles associated with hyperphosphorylated tau protein. AD has been reported as an outcome of multiple probabilistic factors such as age, lifestyle, oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and epigenetics. Epigenetics are heritable changes in gene expression that give a phenotype without altering the DNA sequences. Epigenetic mechanisms include DNA methylation, hydroxymethylation, histone modifications, regulation of miRNAs and long non-coding RNAs, which are reported to be dysregulated in AD. Further, epigenetic mechanisms have been shown as a key player as they regulate memory development, where DNA methylation and post-translational modifications of histone tails are the prime epigenetic markers. Also, alterations of AD-related genes cause pathogenesis on the transcriptional level. In the current chapter, we summarize the role of epigenetics in the onset and progression of AD and the use of epigenetic therapeutics to ameliorate the constraints of AD.

Epigenetic control of heredity.

Epigenetics is the field of science that deals with the study of changes in gene function that do not involve changes in DNA sequence and are heritable while epigenetics inheritance is the process of transmission of epigenetic modifications to the next generation. It can be transient, intergenerational, or transgenerational. There are various epigenetic modifications involving mechanisms such as DNA methylation, histone modification, and noncoding RNA expression, all of which are inheritable. In this chapter, we summarize the information on epigenetic inheritance, its mechanism, inheritance studies on various organisms, factors affecting epigenetic modifications and their inheritance, and the role of epigenetic inheritance in the heritability of diseases.

Aging: Epigenetic modifications.

Aging is one of the most complex and irreversible health conditions characterized by continuous decline in physical/mental activities that eventually poses an increased risk of several diseases and ultimately death. These conditions cannot be ignored by anyone but there are evidences that suggest that exercise, healthy diet and good routines may delay the Aging process significantly. Several studies have demonstrated that Epigenetics plays a key role in Aging and Aging-associated diseases through methylation of DNA, histone modification and non-coding RNA (ncRNA). Comprehension and relevant alterations in these epigenetic modifications can lead to new therapeutic avenues of age-delaying contrivances. These processes affect gene transcription, DNA replication and DNA repair, comprehending epigenetics as a key factor in understanding Aging and developing new avenues for delaying Aging, clinical advancements in ameliorating aging-related diseases and rejuvenating health. In the present article, we have described and advocated the epigenetic role in Aging and associated diseases.

Incidence, Subtypes, Risk factors, and Outcome of Delirium: A Prospective Observational Study from Indian Intensive Care Unit.

Background: Delirium is a common, under-recognized, and often fatal condition in critically ill patients, characterized by acute disorder of attention and cognition. The global prevalence varies with a negative impact on outcomes. A paucity of Indian studies exists that have systematically assessed delirium. Objective: A prospective observational study designed to determine the incidence, subtypes, risk factors, complications, and outcome of delirium in Indian intensive care units (ICUs). Patients and methods: Among 1198 adult patients screened during the study period (December 2019-September 2021), 936 patients were included. The confusion assessment method score (CAM-ICU) and Richmond agitation sedation scale (RASS) were used, with additional confirmation of delirium by the psychiatrist/neurophysician. Risk factors and related complications were compared with a control group. Results: Delirium occurred in 22.11% of critically ill patients. The hypoactive subtype was the most common (44.9%). The risk factors recognized were higher age, increased acute physiology and chronic health evaluation (APACHE-II) score, hyperuricemia, raised creatinine, hypoalbuminemia, hyperbilirubinemia, alcoholism, and smoking. Precipitating factors included patients admitted on noncubicle beds, proximity to the nursing station, requiring ventilation, as well as the use of sedatives, steroids, anticonvulsants, and vasopressors. Complications observed in the delirium group were unintentional removal of catheters (35.7%), aspiration (19.8%), need for reintubation (10.6%), decubitus ulcer formation (18.4%), and high mortality (21.3% vs 5%). Conclusion: Delirium is common in Indian ICUs with a potential effect on length of stay and mortality. Identification of incidence, subtype, and risk factors is the first step toward prevention of this important cognitive dysfunction in the ICU. How to cite this article: Tiwari AM, Zirpe KG, Khan AZ, Gurav SK, Deshmukh AM, Suryawanshi PB, et al. Incidence, Subtypes, Risk factors, and Outcome of Delirium: A Prospective Observational Study from Indian Intensive Care Unit. Indian J Crit Care Med 2023;27(2):111-118.

Synthetic receptors in medicine.

Cellular signaling is controlled by ligand receptor interaction and subsequent biochemical changes inside the cell. Manipulating receptors as per need that can be a strategy to alter the disease pathologies in various conditions. With recent advances in synthetic biology, now it is possible to engineer the artificial receptor "synthetic receptors." Synthetic receptors are the engineering receptors that have potential to alter the disease pathology by altering/manipulating the cellular signaling. Several synthetic receptors are being engineered that have shown positive regulation in several disease conditions. Thus, synthetic receptor-based strategy opens a new avenue in the medical field to cope up with various health issues. The current chapter summarizes updated information about the synthetic receptors and their applications in the medical field.

Feasibility and Efficacy of Sustained Low-Efficiency Dialysis in Critically Ill Children with Severe Acute Kidney Injury.

OBJECTIVES: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children. METHODS: Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography. RESULTS: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died. CONCLUSIONS: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI.

Sirtuins, a key regulator of ageing and age-related neurodegenerative diseases.

Sirtuins are Nicotinamide Adenine Dinucleotide (NAD+) dependent class ІΙΙ histone deacetylases enzymes (HDACs) present from lower to higher organisms such as bacteria (Sulfolobus solfataricus L. major), yeasts (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), humans (Homo sapiens sapiens), even in plants such as rice (Oryza sativa), thale cress (Arabidopsis thaliana), vine (Vitis vinifera L.) tomato (Solanum lycopersicum). Sirtuins play an important role in the regulation of various vital cellular functions during metabolism and ageing. It also plays a neuroprotective role by modulating several biological pathways such as apoptosis, DNA repair, protein aggregation, and inflammatory processes associated with ageing and neurodegenerative diseases. In this review, we have presented an updated Sirtuins and its role in ageing and age-related neurodegenerative diseases (NDDs). Further, this review also describes the therapeutic potential of Sirtuins and the use of Sirtuins inhibitor/activator for altering the NDDs disease pathology.

Supplement Type Impact on the Performance and Nutrient Dynamics of Nursing Does and Kids Raised in Woodlands.

The influence of different supplement types on the performance and nutrient dynamics of goats stocked in woodlands is not known. The objective of this study was to evaluate the effect of supplement type on the performance and the concentration of fecal nutrients of nursing does and the performance of kids raised in woodlands. One group of goats (SG, 9 does; 18 kids) was allowed supplemental grazing in adjacent silvopasture plots for 3-4 h daily and another group (SF, 8 does; 15 kids) was supplemented with corn (0.5% of metabolic weight) and ad libitum hay. Vegetation samples were collected and analyzed for productivity and quality (crude protein, CP; acid detergent fiber, ADF; neutral detergent fiber, NDF). The quality of the hay (N, ADF, NDF) and fecal samples (N, P, Ca) was analyzed. The animals' live weight, FAMACHA score, and body condition score were collected. The browsing height for does consuming woodland vegetation was measured. Data were analyzed using the GLM procedure, Mixed procedure, and MEANS procedure in SAS 9.4. SG does showed better FAMACHA scores vs. SF does (p < 0.05). Fecal N and ADF were greater (p < 0.0001) in SG does vs. SF does. The findings showed a better performance and greater concentration of fecal nutrients in SG does vs. SF does, suggesting grazing quality pastures is a better option than using feedstuffs to supplement nursing does in woodland.